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Deal Watch: AbbVie Adds To Immunology Pipeline Through Deal With OSE - Scrip
NORTH CHICAGO, Ill. and SAN DIEGO, Feb. 22, 2024 /PRNewswire/ -- AbbVie Inc. (NYSE: ABBV) and Tentarix Biotherapeutics today announced a multi-year collaboration focused on the discovery and development of conditionally-active, multi-specific biologic candidates in oncology and immunology. The collaboration will integrate AbbVie's expertise in oncology and immunology with Tentarix's proprietary Tentacles platform.
Tentacles are multi-functional, conditionally-active antibody-based biologics that are designed specifically to activate immune cells that can modulate disease pathways, while potentially mitigating safety concerns associated with non-specific targeting of other immune cells.
"Oncology and immunology are two of our key strategic growth areas where we are pursuing novel technologies that aim to deliver transformative therapies, which address unmet patient needs," said Jonathon Sedgwick, Ph.D., senior vice president and global head of discovery research, AbbVie. "This strategic partnership complements our ongoing efforts in developing novel biologics, potentially to expand our oncology and immunology portfolios with conditionally-active multi-specific molecules."
"We are excited to join forces with AbbVie to help accelerate cutting-edge, conditionally-active therapeutic programs towards clinical applications for patients in need," said Don Santel, interim chief executive officer, Tentarix Biotherapeutics. "This collaboration adds to our portfolio of internal and external pipeline programs and is a strong validation of our approach in understanding and targeting complex immune interactions that drive cancers and inflammatory diseases."
Under the terms of the agreements, Tentarix will receive upfront option payments, totaling $64 million from AbbVie, for the two programs. AbbVie will receive an exclusive option to fully acquire the programs following candidate nomination, for an additional undisclosed payment for each program.
About AbbVieAbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas immunology, oncology, neuroscience, and eye care and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us atwww.abbvie.com. Follow @abbvie onLinkedIn,Facebook,Instagram,X (formerly Twitter), andYouTube.
About TentarixTentarix's mission is to develop first-in-class targeted, multifunctional, conditional therapies across a range of indications of high unmet medical need. Tentarix is focused on modulating cell specific functions while increasing the safety profile for biologics. Tentarix has built a team that aims to transform research and development through understanding complex immune interactions (CellSurf), discovery of novel human antibodies (HuTARG), and high-throughput screening of conditional multi-specifics (FunctionSeq). For more information, please visit http://www.tentarix.com.
AbbVie Forward-Looking StatementsSome statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2023 AnnualReport on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.
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AbbVie and Tentarix Announce Collaboration to Develop Conditionally-Active, Multi-Specific Biologics for Oncology ... - PR Newswire
Arunachalam, P. S. et al. Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans. Science 369, 12101220 (2020).
Article ADS CAS PubMed PubMed Central Google Scholar
Shen-Orr, S. S. & Furman, D. Variability in the immune system: of vaccine responses and immune states. Curr. Opin. Immunol. 25, 542547 (2013).
Article CAS PubMed PubMed Central Google Scholar
Yofe, I., Dahan, R. & Amit, I. Single-cell genomic approaches for developing the next generation of immunotherapies. Nat. Med. 26, 171177 (2020).
Article CAS PubMed Google Scholar
Banchereau, R., Cepika, A.-M. & Pascual, V. Systems approaches to human autoimmune diseases. Curr. Opin. Immunol. 25, 598605 (2013).
Article CAS PubMed PubMed Central Google Scholar
Davis, M. M., Tato, C. M. & Furman, D. Systems immunology: just getting started. Nat. Immunol. 18, 725732 (2017).
Article CAS PubMed PubMed Central Google Scholar
Germain, R. N., Meier-Schellersheim, M., Nita-Lazar, A. & Fraser, I. D. C. Systems biology in immunology: a computational modeling perspective. Annu. Rev. Immunol. 29, 527585 (2011).
Article CAS PubMed PubMed Central Google Scholar
Ma, S. et al. Chromatin potential identified by shared single-cell profiling of RNA and chromatin. Cell 183, 11031116 (2020). This work pioneered paired sequencing of chromatin accessibility and transcriptome in single cells (SHARE-seq).
Article CAS PubMed PubMed Central Google Scholar
Sthl, P. L. et al. Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science 353, 7882 (2016). This work pioneered spatially resolved transcriptomics.
Article ADS PubMed Google Scholar
Regev, A. et al. The Human Cell Atlas. eLife https://doi.org/10.7554/eLife.27041 (2017).
Domnguez Conde, C. et al. Cross-tissue immune cell analysis reveals tissue-specific features in humans. Science 376, eabl5197 (2022).
Article PubMed PubMed Central Google Scholar
HuBMAP Consortium. The human body at cellular resolution: the NIH Human Biomolecular Atlas Program. Nature 574, 187192 (2019).
Article ADS CAS Google Scholar
Martin, F. J. et al. Ensembl 2023. Nucleic Acids Res. 51, D933D941 (2023).
Article CAS PubMed Google Scholar
UniProt Consortium. Uniprot: the universal protein knowledgebase in 2023. Nucleic Acids Res. 51, D523D531 (2023).
Article Google Scholar
Trei, D. et al. Integrated intra and intercellular signaling knowledge for multicellular omics analysis. Mol. Syst. Biol. 17, e9923 (2021). This work introduces a comprehensive meta-resource that collects data from over a hundred databases, including, for example, protein interaction networks, ligandreceptor annotations and protein complex information.
Article PubMed PubMed Central Google Scholar
Szklarczyk, D. et al. STITCH 5: augmenting protein-chemical interaction networks with tissue and affinity data. Nucleic Acids Res. 44, D380D384 (2016).
Article CAS PubMed Google Scholar
Garcia-Alonso, L., Holland, C. H., Ibrahim, M. M., Turei, D. & Saez-Rodriguez, J. Benchmark and integration of resources for the estimation of human transcription factor activities. Genome Res. 29, 13631375 (2019).
Article CAS PubMed PubMed Central Google Scholar
Schubert, M. et al. Perturbation-response genes reveal signaling footprints in cancer gene expression. Nat. Commun. 9, 20 (2018).
Article ADS PubMed PubMed Central Google Scholar
Armingol, E., Officer, A., Harismendy, O. & Lewis, N. E. Deciphering cell-cell interactions and communication from gene expression. Nat. Rev. Genet. 22, 7188 (2021).
Article CAS PubMed Google Scholar
Vandereyken, K., Sifrim, A., Thienpont, B. & Voet, T. Methods and applications for single-cell and spatial multi-omics. Nat. Rev. Genet. 24, 494515 (2023).
Article CAS PubMed Google Scholar
Baysoy, A., Bai, Z., Satija, R. & Fan, R. The technological landscape and applications of single-cell multi-omics. Nat. Rev. Mol. Cell Biol. 24, 695713 (2023).
Article CAS PubMed Google Scholar
Bonaguro, L. et al. A guide to systems-level immunomics. Nat. Immunol. 23, 14121423 (2022).
Article CAS PubMed Google Scholar
Stuart, T. et al. Comprehensive integration of single-cell data. Cell 177, 18881902 (2019).
Article CAS PubMed PubMed Central Google Scholar
Heumos, L. et al. Best practices for single-cell analysis across modalities. Nat. Rev. Genet. 24, 550572 (2023).
Article CAS PubMed Google Scholar
Amezquita, R. A. et al. Orchestrating single-cell analysis with Bioconductor. Nat. Methods 17, 137145 (2020).
Article CAS PubMed Google Scholar
Gene Ontology Consortium et al. The Gene Ontology knowledgebase in 2023. Genetics 224, iyad031 (2023).
Kanehisa, M., Furumichi, M., Sato, Y., Kawashima, M. & Ishiguro-Watanabe, M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 51, D587D592 (2023).
Article CAS PubMed Google Scholar
Gillespie, M. et al. The reactome pathway knowledgebase 2022. Nucleic Acids Res. 50, D687D692 (2022).
Article CAS PubMed Google Scholar
Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 1554515550 (2005).
Article ADS CAS PubMed PubMed Central Google Scholar
Vremo, L., Nielsen, J. & Nookaew, I. Enriching the gene set analysis of genome-wide data by incorporating directionality of gene expression and combining statistical hypotheses and methods. Nucleic Acids Res. 41, 43784391 (2013).
Article PubMed PubMed Central Google Scholar
Badia-I-Mompel, P. et al. decoupleR: ensemble of computational methods to infer biological activities from omics data. Bioinform. Adv. 2, vbac016 (2022).
Article PubMed PubMed Central Google Scholar
Hosokawa, H. & Rothenberg, E. V. How transcription factors drive choice of the T cell fate. Nat. Rev. Immunol. 21, 162176 (2021).
Article CAS PubMed Google Scholar
Kawasaki, T. & Kawai, T. Toll-like receptor signaling pathways. Front. Immunol. 5, 461 (2014).
Article PubMed PubMed Central Google Scholar
Saini, A., Ghoneim, H. E., Lio, C. -W. J., Collins, P. L. & Oltz, E. M. Gene regulatory circuits in innate and adaptive immune cells. Annu. Rev. Immunol. 40, 387411 (2022).
Article CAS PubMed PubMed Central Google Scholar
Liu, Z.-P., Wu, C., Miao, H. & Wu, H. RegNetwork: an integrated database of transcriptional and post-transcriptional regulatory networks in human and mouse. Database 2015, bav095 (2015).
Article PubMed PubMed Central Google Scholar
Keenan, A. B. et al. ChEA3: transcription factor enrichment analysis by orthogonal omics integration. Nucleic Acids Res. 47, W212W224 (2019).
Article CAS PubMed PubMed Central Google Scholar
Mller-Dott, S. et al. Expanding the coverage of regulons from high-confidence prior knowledge for accurate estimation of transcription factor activities. Nucleic Acids Res. 51, 1093410949 (2023).
Article PubMed PubMed Central Google Scholar
Holland, C. H. et al. Robustness and applicability of transcription factor and pathway analysis tools on single-cell RNA-seq data. Genome Biol. 21, 36 (2020).
Article CAS PubMed PubMed Central Google Scholar
Zeitlinger, J. Seven myths of how transcription factors read the cis-regulatory code. Curr. Opin. Syst. Biol. 23, 2231 (2020).
Article PubMed PubMed Central Google Scholar
Fiers, M. W. E. J. et al. Mapping gene regulatory networks from single-cell omics data. Brief. Funct. Genomics 17, 246254 (2018).
Article CAS PubMed PubMed Central Google Scholar
Chen, S. & Mar, J. C. Evaluating methods of inferring gene regulatory networks highlights their lack of performance for single cell gene expression data. BMC Bioinformatics 19, 232 (2018).
Article PubMed PubMed Central Google Scholar
Pratapa, A., Jalihal, A. P., Law, J. N., Bharadwaj, A. & Murali, T. M. Benchmarking algorithms for gene regulatory network inference from single-cell transcriptomic data. Nat. Methods 17, 147154 (2020).
Article CAS PubMed PubMed Central Google Scholar
Badia-I-Mompel, P. et al. Gene regulatory network inference in the era of single-cell multi-omics. Nat. Rev. Genet. 24, 739754 (2023).
Article CAS PubMed Google Scholar
Wayman, J. A. et al. An atlas of gene regulatory networks for memory CD4+ T cells in youth and old age. Preprint at BioRxiv https://doi.org/10.1101/2023.03.07.531590 (2023).
Chowdhary, K. & Benoist, C. A variegated model of transcription factor function in the immune system. Trends Immunol. 44, 530541 (2023).
Article CAS PubMed Google Scholar
Bravo Gonzlez-Blas, C. et al. SCENIC+: single-cell multiomic inference of enhancers and gene regulatory networks. Nat. Methods 20, 13551367 (2023).
Article PubMed PubMed Central Google Scholar
Kramer, B. A., Sarabia Del Castillo, J. & Pelkmans, L. Multimodal perception links cellular state to decision-making in single cells. Science 377, 642648 (2022).
Article ADS CAS PubMed Google Scholar
Weidemller, P., Kholmatov, M., Petsalaki, E. & Zaugg, J. B. Transcription factors: bridge between cell signaling and gene regulation. Proteomics 21, e2000034 (2021).
Article PubMed Google Scholar
Deribe, Y. L., Pawson, T. & Dikic, I. Post-translational modifications in signal integration. Nat. Struct. Mol. Biol. 17, 666672 (2010).
Article CAS PubMed Google Scholar
Lun, X. -K. & Bodenmiller, B. Profiling cell signaling networks at single-cell resolution. Mol. Cell. Proteom. 19, 744756 (2020).
Article CAS Google Scholar
Dugourd, A. & Saez-Rodriguez, J. Footprint-based functional analysis of multiomic data. Curr. Opin. Syst. Biol. 15, 8290 (2019).
Article PubMed PubMed Central Google Scholar
Rydenfelt, M., Klinger, B., Klnemann, M. & Blthgen, N. SPEED2: inferring upstream pathway activity from differential gene expression. Nucleic Acids Res. 48, W307W312 (2020).
Article CAS PubMed PubMed Central Google Scholar
Jiang, P. et al. Systematic investigation of cytokine signaling activity at the tissue and single-cell levels. Nat. Methods 18, 11811191 (2021). This work introduced a comprehensive resource describing how cytokines affect gene expression, which can be used to infer cytokine activity from transcriptomics data.
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Integrating single-cell multi-omics and prior biological knowledge for a functional characterization of the immune system - Nature.com
Cooper recently won the Albert Lasker Award, known as Americas Nobel Prize, given to the living person considered to have made the greatest contribution to medical science.
Max Cooper, M.D., Photo Credit: Emory UniversityMax Cooper, M.D., a distinguished immunologist and 40-year career veteran of the University of Alabama at Birmingham, will return to UAB on March 11 to present this years 36th Bertram M. Marx Endowed Lecture, hosted by the UAB Department of Microbiology.
Cooper is known for his research characterizing T cells and B cells and his numerous unprecedented contributions to the field of immunology.
Dr. Cooper is a towering figure in the field of immunology, said J. Victor Garcia-Martinez, Ph.D., chair of the UAB Department of Microbiology. He literally wrote the book on B cell biology and the adaptive immune system. His discoveries have transcended generations of scientists, and his impact has shaped modern immunology in numerous ways. He is an outstanding role model for young scientists.
Cooper, a professor in the Department of Pathology and Laboratory Medicine and the Emory Vaccine Center at the Emory University School of Medicine, came to UAB in 1967 as a professor in the Division of Pediatric Allergy and Immunology of the Department of Pediatrics and as an associate professor in the Department of Microbiology.
He went on to become a professor in the Department of Microbiology and was also involved with UABs ONeal Comprehensive Cancer Center, the Comprehensive Arthritis, Musculoskeletal, Bone and Autoimmunity Center, and the Cystic Fibrosis Research Center.
Cooper moved to Emory University in 2008 but remains a professor emeritus of Medicine at UAB. He is also an Emory University School of Medicine Eminent Scholar, Georgia Research Alliance investigator and investigator at the Emory Center for AIDS Research.
Among his many notable awards, Cooper became UABs first member of the National Academy of Sciences in 1988 and was named to the National Academy of Medicine in 1990. He received the American Association of Immunologists Lifetime Achievement Award in 2000, was inducted as a foreign member of the British Royal Society in 2017 and received the Japan Prize in 2018.
In 2019, Cooper, together with Jacques Miller, was awarded the Albert Lasker Award for Basic Medical Research, an award that frequently precedes a Nobel Prize in Medicine. The Lasker Award, known as Americas Nobel Prize, is given by the Lasker Foundation to the living person considered to have made the greatest contribution to medical science.
Dr. Max Coopers contributions to the field of immunology and medicine at large characterize him among the most distinguished scientists to have called UAB home, said Anupam Agarwal, M.D., senior vice president for Medicine and dean of the Marnix E. Heersink School of Medicine. I am thrilled that he is returning to share his invaluable insights with the UAB research community.
The 36th Bertram M. Marx Lectureship will take place Monday, March 11, at 3 p.m. in-person in Room 102, the Cudworth Building. Cooper will present Evolution of Lymphocyte-Based Immunity. A reception will follow in the Bevill Biomedical Research Building lobby.
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Renowned immunologist and four-decade UAB researcher Max Cooper, M.D., will deliver this year's Marx Lecture - University of Alabama at Birmingham
Chong EA, Melenhorst JJ, Lacey SF, Ambrose DE, Gonzalez V, Levine BL, et al. PD-1 blockade modulates chimeric antigen receptor (CAR)-modified T cells: refueling the CAR. Blood. 2017;129:103941.
Article CAS PubMed PubMed Central Google Scholar
Bell M, Gottschalk S. Engineered cytokine signaling to improve CAR T cell effector function. Front Immunol. 2021;12:684642.
Article CAS PubMed PubMed Central Google Scholar
Travis MA, Sheppard D. TGF- activation and function in immunity. Annu Rev Immunol. 2014;32:5182.
Article CAS PubMed Google Scholar
Wieser R, Attisano L, Wrana JL, Massagu J. Signaling activity of transforming growth factor beta type II receptors lacking specific domains in the cytoplasmic region. Mol Cell Biol. 1993;13:723947.
CAS PubMed PubMed Central Google Scholar
Gorelik L, Flavell RA. Abrogation of TGFbeta signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity. 2000;12:17181.
Article CAS PubMed Google Scholar
Gorelik L, Flavell RA. Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells. Nat Med. 2001;7:111822.
Article CAS PubMed Google Scholar
Kloss CC, Lee J, Zhang A, Chen F, Melenhorst JJ, Lacey SF, et al. Dominant-negative TGF- receptor enhances PSMA-targeted human CAR T cell proliferation and augments prostate cancer eradication. Mol Ther. 2018;26:185566.
Article CAS PubMed PubMed Central Google Scholar
Noh KE, Lee JH, Choi SY, Jung NC, Nam JH, Oh JS, et al. TGF-/IL-7 chimeric switch receptor-expressing CAR-T cells inhibit recurrence of CD19-positive B cell lymphoma. Int J Mol Sci. 2021;22:8706.
Article CAS PubMed PubMed Central Google Scholar
Tang N, Cheng C, Zhang X, Qiao M, Li N, Mu W, et al. TGF- inhibition via CRISPR promotes the long-term efficacy of CAR T cells against solid tumors. JCI Insight. 2020;5:e133977.
Article PubMed PubMed Central Google Scholar
Narayan V, Barber-Rotenberg JS, Jung IY, Lacey SF, Rech AJ, Davis MM, et al. PSMA-targeting TGF-insensitive armored CAR Tcells in metastatic castration-resistant prostate cancer: a phase 1 trial. Nat Med. 2022;28:72434.
Article CAS PubMed PubMed Central Google Scholar
Liang, S, Zheng R, Zuo B, Li J, Wang Y, Han Y, et al. SMAD7 expression improves the persistent and safety of CAR T cells for solid tumors. Cell Mol Immunol. 2024;21:21326.
Hong S, Lim S, Li AG, Lee C, Lee YS, Lee EK, et al. Smad7 binds to the adaptors TAB2 and TAB3 to block recruitment of the kinase TAK1 to the adaptor TRAF2. Nat Immunol. 2007;8:50413.
Article CAS PubMed Google Scholar
Li G, Liao G, Xie J, Liu B, Li X, Qiu M. Overexpression of SMAD7 improves the function of EGFR-targeted human CAR-T cells against non-small-cell lung cancer. Respirology. 2023;28:86980.
Article PubMed Google Scholar
Tu E, Chia C, Chen W, Zhang D, Park SA, Jin W, et al. T cell receptor-regulated TGF- type I receptor expression determines T cell quiescence and activation. Immunity. 2018;48:74559.e6.
Article CAS PubMed PubMed Central Google Scholar
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Inactivation of TGF- signaling in CAR-T cells | Cellular & Molecular Immunology - Nature.com
Scientists have long believed that a newborns immune system was an immature version of an adults, but new research shows that newborns T cells white blood cells that protect from disease outperform those of adults at fighting off numerous infections.
These results help clarify why adults and infants respond differently to infectionsand pave the way for controlling T cells behavior for therapeutic applications.
This discovery was described in a paper, The Gene Regulatory Basis of Bystander Activation in CD8+ T cells, which published Feb. 23 in the journal Science Immunology. Brian Rudd, associate professor in the Department of Microbiology and Immunology in the College of Veterinary Medicine, and Andrew Grimson, professor in the Department of Molecular Biology and Genetics (College of Arts and Sciences), co-led the study.
The immune system is almost always viewed from an adult perspective, Rudd said. For example, adult T cells outperform newborn T cells at tasks including recognizing antigens, forming immunological memory and responding to repeat infections, which has led to the belief that infants T cells were just a weaker version of the adult ones. But during the COVID-19 pandemic, many were surprised by the apparent lack of illness in infants, bringing this long-standing belief into question.
Interested in understanding these age-related differences, Rudd and Grimson discovered that newborn T cells are not deficient. Instead, they are involved in a part of the immune system that does not require antigen recognition, the innate arm of the immune system. While adults T cells use adaptive immunity recognizing specific germs to then fight them later newborn T cells are activated by proteins associated with innate immunity, the part of the immune system that offers rapid but nonspecific protection against microbes the body has never encountered.
Our paper demonstrates that neonatal T cells are not impaired, they are just different than adult T cells and these differences likely reflect the type of functions that are most useful to the host at distinct stages of life, Rudd said.
Neonatal T cells can participate in the innate arm of the immune system. This enables newborns T cells to do something that most adult T cells cannot respond during the very first stages of an infection and defend against a wide variety of unknown bacteria, parasites and viruses.
We know that neonatal T cells dont protect as well as adult T cells against repeat infections with the same pathogen. But neonatal T cells actually have an enhanced ability to protect the host against early stages of an initial infection, Rudd said. So, it is not possible to say adult T cells are better than neonatal T cells or neonatal T cells are better than adult T cells. They just have different functions.
The team also found that these innate neonatal T cells persist into adulthood in both mice and humans and play unique roles during infection. The team believes that in adults, these neonatal T cells may respond to inflammation that occurs during an infection, in cancer and in autoimmune diseases.
As part of their research, Rudd and his collaborators identified the molecular mechanisms that allow T cells to respond to inflammation and switch between innate and adaptive functions.
We now know the key epigenetic and transcriptional programs that distinguish neonatal T cells from adult T cells at the individual cell level, Rudd said. This knowledge is essential to developing medical applications for controlling T cells behavior in specific ways.
The technology that is now available to study gene regulation of immune cells at the single-cell level allowed Rudd and Grimson to provide new insight into a poorly understood biological process at a very in-depth level.
Being able to go from observing a unique function of T cells to a molecular mechanism is really exciting, Rudd said. And this was possible because we were able to combine the expertise in cellular and developmental immunology in my lab with the tools to study gene regulation in Andrews lab.
Following up on his discovery, Rudd wants to study the neonatal T cells that persist into adulthood in humans. We are also interested in studying how changes in the relative numbers of neonatal T cells in adults contributes to variation in the susceptibility to infection and outcomes to disease, he said.
The large, multi-institution project also included collaborators at University of Rochester and University of Washington.
This work was supported by the National Institute of Allergy and Infectious Disease and the National Institute of Child Health and Human Development, in the National Institutes of Health.
Elodie Smith is a writer for the College of Veterinary Medicine.
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Babies use their immune system differently but efficiently | Cornell Chronicle - Cornell Chronicle
News Release
Sunday, February 25, 2024
Drug can help protect kids with multiple food allergies during accidental exposure.
A 16-week course of a monoclonal antibody, omalizumab, increased the amount of peanut, tree nuts, egg, milk and wheat that multi-food allergic children as young as 1 year could consume without an allergic reaction in a late-stage clinical trial. Nearly 67% of participants who completed the antibody treatment could consume a single dose of 600 milligrams (mg) or more of peanut protein, equivalent to 2.5 peanuts, without a moderate or severe allergic reaction, in contrast with less than 7% of participants who received placebo. The treatment yielded similar outcomes for egg, milk, wheat, cashew, walnut and hazelnut at a threshold dose of 1,000 mg protein or more. This suggests the antibody therapy has the potential to protect children and adolescents if they accidentally eat a food to which they are allergic despite efforts to avoid it, according to the investigators. The findings were presented today at the American Academy of Allergy, Asthma & Immunology Annual Meeting in Washington, D.C., and published in The New England Journal of Medicine.
People with food allergies and their caregivers need to maintain constant vigilance to avoid foods that could cause a potentially life-threatening allergic reaction. This is extremely stressful, especially for parents of young children, said Jeanne Marrazzo, M.D., M.P.H., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health and the trials regulatory sponsor. Although food avoidance remains critical, the findings reported today show that a medicine can help reduce the risk of allergic reactions to common foods and may provide protection from accidental exposure emergencies.
NIAID funds the ongoing trial with additional support from and collaboration with Genentech, a member of the Roche Group, and Novartis Pharmaceuticals Corporation. The two companies collaborate to develop and promote omalizumab, marketed as Xolair, and are supplying it for the trial. The National Center for Advancing Translational Sciences, also part of NIH, supports some of the staff, space and services used to conduct the trial.
An estimated 7.6% of children in the United State roughly 5.5 million kids have food allergies. On February 16, 2024, the Food and Drug Administration approved omalizumab for the reduction of allergic reactions, including anaphylaxis, that may occur with an accidental exposure to one or more foods in adults and children aged 1 year and older with food allergy. The FDA approval was based on data from a planned interim analysis of the Phase 3 NIAID trial. People taking omalizumab still need to avoid foods they are allergic to. Omalizumab is not approved for the emergency treatment of allergic reactions, including anaphylaxis.
Previously, the only available treatment for food allergy was oral immunotherapy, or OIT, which involves daily ingestion of a specific food allergen in gradually increasing doses up to a maintenance amount.
The multi-stage trial is called Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen OIT in Food Allergic Children and Adults, or OUtMATCH. The first stage of the study was designed to see if taking omalizumab increased the threshold for the amount of food that caused allergic reactions, thereby reducing the likelihood of reactions to small amounts of food allergens during accidental exposure.
Omalizumab works by binding to the allergy-causing antibody called immunoglobulin E in the blood and preventing it from arming key immune cells responsible for allergic reactions. This renders these cells much less sensitive to stimulation by any allergen.
The NIAID-funded Consortium for Food Allergy Research (CoFAR) is conducting OUtMATCH at 10 locations across the United States. The CoFAR has enrolled 177 children and adolescents ages 1 to 17 years and three adults ages 18 to 55 years, all with confirmed allergy to peanut and at least two other common foods among milk, egg, cashew, wheat, hazelnut or walnut.
In the first stage of the trial, people who reacted to small amounts of food allergens during oral food challenges were assigned at random to receive injections of either omalizumab or placebo. Neither the participants nor the investigators knew which food was used in a challenge nor who was in which group. After 16 to 20 weeks of injections, the participants were challenged again in a carefully controlled setting to see if they could tolerate a greater amount of food than they did at the outset. The goal was to find out if omalizumab injections led to a statistically significant increase in the proportion of participants who could consume roughly the equivalent of 2.5 peanuts without a moderate or severe allergic reaction, up from less than half a peanut at the outset, and similarly greater quantities of milk, egg or cashew among people allergic to those foods.
Investigators found that omalizumab was superior to placebo in increasing the reaction threshold for peanut, milk, egg and cashew as well as wheat, walnut and hazelnut to levels that likely would protect against allergic reactions upon accidental exposure. Seventy-nine of 118 omalizumab-treated children and adolescents, or 66.9%, could consume at least a single dose of 600 mg or more of peanut protein without a moderate or severe allergic reaction during the post-treatment challenge, in contrast with four out of 59 children and adolescents, or 6.8%, who received placebo. The researchers observed similar results for milk, egg, cashew, wheat, walnut and hazelnut at a threshold dose of 1,000 mg protein or more.
Many omalizumab-treated participants ate more than 600 mg of peanut protein without a moderate or severe allergic reaction. Sixty-seven percent consumed a cumulative dose of 1,044 mg of peanut protein, or about four peanuts, and 44% ate a cumulative dose of 6,044 mg of peanut protein, or about 25 peanuts. In addition, substantial proportions of treated participants consumed a cumulative dose of 1,044 mg of more than one food without a moderate or severe allergic reaction. Sixty-nine percent ate this amount of two foods, and 47%, three foods.
The first 60 participants who completed the first stage entered a 24-week open-label extension of omalizumab injections followed by additional oral food challenges. Most participants who had received omalizumab in the first stage maintained or increased the amount of food protein they could consume without an allergic reaction during the extension.
Robert Wood, M.D., and Sharon Chinthrajah, M.D. are leading the trial. Dr. Wood is the Julie and Neil Reinhard Professor of Pediatric Allergy and Immunology and director of the Pediatric Clinical Research Unit at the Johns Hopkins University School of Medicine. Dr. Chinthrajah is an associate professor of medicine and of pediatric allergy and clinical immunology at Stanford University School of Medicine.
Further information about the ongoing OUtMATCH trial is available at ClinicalTrials.gov under study identifier NCT03881696. The outcomes of later stages of the trial will be published in the future.
NIAID conducts and supports researchat NIH, throughout the United States, and worldwideto study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.
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RA Wood, et al. Omalizumab for the treatment of multiple food allergy. The New England Journal of Medicine DOI: 10.1056/NEJMoa2312382. (2024).
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Antibody reduces allergic reactions to multiple foods in NIH clinical trial - National Institutes of Health (NIH) (.gov)
CAMBRIDGE, United Kingdom, Feb. 20, 2024 (GLOBE NEWSWIRE) -- Mestag Therapeutics (Mestag), a biotech company harnessing new insights into fibroblast-immune interactions to develop impactful treatments for patients, today announced the appointments of additional distinguished, world-leading advisors to guide the development of its lead program M300, a first-in-class antibody program designed to conditionally induce the formation of Tertiary Lymphoid Structures (TLS) in the tumor.
The new appointments expand Mestags advisors and comprise a unique group of investigators with extensive experience in the development of novel cancer therapies and specific expertise in the field of TLS biology in cancer. TLSs are aggregates of immune cells which provide a site of entry and education for immune cells in the tumor. The presence of TLS in tumors has recently become recognized as strongly predictive of improved patient outcomes and better response to therapy.1,2,3,4
Susan Hill, PhD, Chief Executive Officer of Mestag Therapeutics, said, Mestags M300 program opens up a new paradigm for the treatment of solid tumors. Advances in understanding TLS biology in cancer, and the associated benefit to patient outcomes, have enabled us to design a first-in-class program with the potential to benefit large numbers of patients with cancer. We are honored to work with such an eminent group of experts in this field to drive the program urgently into the clinic.
The newly appointed M300 advisors comprise Prof. Gabriele Bergers, group leader at the Flanders Institute for Biotechnology (VIB) Center for Cancer Biology and Professor of Oncology at the University of Leuven in Leuven, Belgium; Prof. Julie R. Brahmer, Director of the Thoracic Oncology Program, Professor of Oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, as well as the Marilyn Meyerhoff Professor in Thoracic Oncology; Prof. Jeffrey L. Browning, Research Professor at the Boston University School of Medicine in the Departments of Virology, Immunology and Microbiology and Rheumatology; Prof. Wolf H. Fridman, Professor Emeritus of Immunology at Universit Paris-Cit, France; Prof. Catherine Sauts-Fridman, Professor Emeritus at Universit Paris-Cit; Prof. Elizabeth M. Jaffee, Professor of Oncology and Deputy Director at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; and Prof. Ignacio Melero, Professor of Immunology at the Academic Hospital of Navarra and at the Center for Applied Medical Research (CIMA) of the University of Navarra.
Ignacio Melero, MD, PhD, advisor to Mestag and Professor of Immunology at the Academic Hospital of Navarra and at the Center for Applied Medical Research (CIMA) of the University of Navarra, said, I look forward to collaborating with Mestag and to be a part of their world-class advisory team. I believe there is potential to develop transformative therapies for patients battling cancer. Mestags novel approach leverages known immunobiology, which for the first time, is being translationally harnessed to stimulate an anti-cancer immune environment within cancer tissue. Recent evidence supports the beneficial role of tertiary lymphoid structures in cancer, and the ability of a therapy to safely increase their presence could result in an efficacious intervention in patients with solid tumors.
Biographical information
Gabriele Bergers, PhD, is a Professor of Oncology at the University of Leuven and a group leader at the Vlaams Instituut voor Biotechnologie (VIB)-Center for Cancer Biology in Leuven since 2016.Before her move to the VIB, shewas a Professor in the Department of Neurological Surgery and a PI in the Brain Tumor Research Center (BTRC) at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco (UCSF), for 20 years. She has made seminal discoveries aboutperivasculartumor niches regarding the vasculature andtheimmune cell compartmentin regulating neovascularization, inflammation, and TLS formation in cancer and in revealing and understanding intrinsic and evasive resistance mechanisms of tumors to antiangiogenic immunotherapies. Dr. Bergers has received awards, including the Sidney Kimmel, the Sandler Opportunity, UCSF Breakthrough Biomedical Research, and the Judah Folkman. She hasacted as anexternal advisory board member fora number ofuniversities and pharmaceutical companies. Dr. Bergers wasthe Co-director of the Tumor Microenvironment Brain Tumor Center at UCSF and an advisor to the Max-Planck-Institute for Biomedicine in Muenster, Germany.She was a scientific co-founder of Oncurious.
Julie R. Brahmer, MD, is the Director of the Thoracic Oncology Program, Professor of Oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, co-Leader of Cancer Immunology, as well as the Marilyn Meyerhoff Professor in Thoracic Oncology. She also directs the Kimmel Cancer Center on the Johns Hopkins Bayview campus and is co-principal investigator on Johns Hopkins' National Clinical Trials Network (NCTN) cooperative group grant. Dr. Brahmer is an active clinical leader in the treatment of lung cancer and mesothelioma. Dr. Brahmer's research and clinical practice focuses on the development of new therapies for the treatment of lung cancer and mesothelioma. She is a member of the American Society of Clinical Oncology, serves on the board of directors of the Society of Immunotherapy for Cancer, and is the Chair of the Eastern Cooperative Oncology Group (ECOG) Thoracic Committee. She is also on the medical advisory board of several lung cancer patient advocacy groups including LUNGevity, the Lung Cancer Research Fund, and Lung Cancer Research Foundation of America.
Jeffrey L. Browning, PhD, is a Research Professor at the Boston University School of Medicine in the Departments of Virology, Immunology and Microbiology and Rheumatology. He has a PhD in biochemistry from the University of Wisconsin. As a research scientist in the immunobiology discovery group at Biogen from 1984 to 2012, he centered on the tumor necrosis factor (TNF) family of regulatory molecules, including the discovery of the lymphotoxin, B-cell activating factor (BAFF) and TNF-like weak inducer of apoptosis (TWEAK) systems, and translation of modulators of the lymphotoxin pathway to the clinic in indications ranging from autoimmune disease and inflammatory bowel disease to oncology. He joined Boston University School of Medicine in 2013, with a current focus on altered vascular and stromal states in the perivascular compartment in the skin of systemic sclerosis and lupus patients and the impact on the pathology. Early in his career, he undertook postdoctoral work in the biophysics department of the University of Basel, Switzerland, using nuclear magnetic resonance to study membrane structure; and in the neurobiology department at the University of California, San Francisco researching the neuromuscular junction.
Wolf H. Fridman, MD, is Professor Emeritus of Immunology at Universit Paris-Cit. He is an expert in analysis of the tumor microenvironment, demonstrating that context, including functionality, location and density of the immune infiltrate in colorectal tumors, is the major prognostic factor for human cancers. He is involved in developing bioinformatic tools to quantify tumor microenvironment cells used to predict prognosis and immunotherapeutic responses in renal cell and colorectal cancers and sarcomas. His immune classification of soft tissue sarcoma tumors helped demonstrate that TLS and B cell signatures predict favorable clinical outcomes and therapeutic responses to anti-PD-1 therapy better than T cells, findings recently extended to other cancers treated with immune checkpoint blockers. These showed plasma cells generated inside TLS produce anti-tumor antibodies associated with a patients response to immunotherapy, opening the way for novel immune-based tools for efficient prognosis and therapy.
Catherine Sauts-Fridman, PhD, is Professor Emeritus at Universit Paris-Cit. She is the former Director of the Cancer, Immunology and Immunopathology department and Director of the Immunotherapy and Cancer team at Centre de Recherche des Cordeliers. Her research focuses on the heterogeneity of the immune and inflammatory components of the tumor microenvironment to identify new prognostic and theranostic markers. She carried out work in several fields: histocompatibility antigens, demonstration of the association of human leukocyte antigens (HLAs) with beta2-microglobulin and description of the 3rd histocompatibility locus in mice, H-2L and HLA-C in man, receptors for immunoglobulin G antibodies (biological activity and 3D structure), immuno-oncology (role of interleukin-17, TIME profiles of patients at risk of disease progression in localized kidney cancers, role of Tertiary Lymphoid Structures). She is the former President of the French Society of Immunology and European Federation of Immunological Societies. She founded the EFIS-EJI Ita Askonas Award to acknowledge female group leaders in immunology, and she founded the first European Congress of Immunology. She is Editor-in-Chief of La Revue Immunit et Cancer.
Elizabeth M. Jaffee, MD, is an internationally recognized expert in cancer immunology and pancreatic cancer. She is Deputy Director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Co-Director of the Skip Viragh Pancreatic Cancer Center, and Associate Director of the Bloomberg Kimmel Institute for Cancer Immunotherapy. Her research focus is on developing novel immunotherapies for the treatment and prevention of pancreatic cancer. Prof. Jaffee is a past President of AACR and has served on several committees at the National Cancer Institute. She is Chief Medical Advisor to the Lustgarten Foundation for Pancreatic Cancer Research, and the Inaugural Director of the Convergence Institute for Integrating Technologies and Computational Sciences at Johns Hopkins. She is Chair of President Bidens Cancer Panel.
Ignacio Melero, MD, PhD, is Professor of Immunology at the Academic Hospital of Navarra and at the Center for Applied Medical Research (CIMA) of the University of Navarra. He leads a group working in translational tumor immunotherapy with an emphasis on cell therapy, cytokine gene therapy, and immune-stimulatory monoclonal antibodies. Earlier in his career, Dr. Melero contributed to seminal discoveries in the function of Natural Killer cells, and T-cell co-stimulation via CD137 (4-1BB). Dr. Melero has been awarded the BIAL Prize of Medicine, the Conde de Cartagena Award from the Royal Academy of Medicine, Doctor Durantez LAIR Foundation Award and a CRI research award. He has served on advisory boards of Bristol Myers-Squibb, Roche-Genentech, AstraZeneca, Merck Serono and Boehringer Ingelheim, and holds research grants by Pfizer, Bristol Myers Squibb, and Alligator.
About Mestags M300 Program
M300 is a first-in-class antibody program designed to conditionally induce the formation of Tertiary Lymphoid Structures (TLS) in the tumor. TLSs are aggregates of immune cells that form in tumor tissue as part of our bodies natural anti-cancer mechanisms, and drive powerful immune responses by recruiting, educating, and activating new anti-tumor T and B-cells. Fibroblast populations play a key role in the induction and maintenance of TLSs. TLSs in tumors are strongly predictive of both improved patient outcomes across solid tumor types and better response to therapy.1,2,3,4
About Mestag Therapeutics
Mestag harnesses new insights into fibroblast-immune interactions to develop impactful treatments for patients. We are progressing a pipeline of sophisticated first-in-class antibodies designed to improve the lives of patients with cancer and inflammatory disease. Together with our collaboration partner Janssen Biotech, Inc., a Johnson & Johnson company, we are also identifying novel targets for future therapies.
Our founding investigators comprise global experts in inflammatory disease, cancer, computational biology and fibroblast biology from the University of Oxford, Brigham & Womens Hospital, Harvard Medical School and Cold Spring Harbor Laboratory. We are supported by leading life science investors SV Health Investors, Johnson & Johnson Innovation JJDC, Inc., Forbion, GV (formerly Google Ventures) and Northpond Ventures.
Mestag is headquartered in Cambridge, UK, and in 2021 was recognized on the Fierce 15 list of innovative biotechnology companies.
For further information please visit our website http://www.mestagtherapeutics.com
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Like other factors such as age, sex and genetics, smoking has a major impact on immune responses. This is the finding recently made by a team of scientists at the Institut Pasteur using the Milieu Intrieur cohort of 1,000 healthy volunteers, established to understand variability in immune responses. In addition to its short-term impact on immunity, smoking also has long-term consequences. For many years after they have quit the habit, smokers are left with effects on some of their bodies' defense mechanisms acquired while smoking. These findings, which for the first time reveal a long-term memory of the effects of smoking on immunity, were published in the journal Nature on February 14, 2024.
Individuals' immune systems vary significantly in terms of how effectively they respond to microbial attacks. But how can this variability be explained? What factors cause these differences? "To answer this key question, we set up the Milieu Intrieur cohort comprising 1,000 healthy individuals aged 20 to 70 in 2011," comments Darragh Duffy, Head of the Translational Immunology Unit at the Institut Pasteur and last author of the study. While certain factors such as age, sex and genetics are known to have a significant impact on the immune system, the aim of this new study was to identify which other factors had the most influence."
The scientists exposed blood samples taken from individuals in the Milieu Intrieur cohort to a wide variety of microbes (viruses, bacteria, etc.) and observed their immune response by measuring levels of secreted cytokines(1). Using the large quantities of data gathered for individuals in the cohort, the team then determined which of the 136 investigated variables (body mass index, smoking, number of hours' sleep, exercise, childhood illnesses, vaccinations, living environment, etc.) had the most influence on the immune responses studied. Three variables stood out: smoking, latent cytomegalovirus infection(2) and body mass index. "The influence of these three factors on certain immune responses could be equal to that of age, sex or genetics," points out Darragh Duffy.
As regards smoking, an analysis of the data showed that the inflammatory response, which is immediately triggered by infection with a pathogen, was heightened in smokers, and moreover, the activity of certain cells involved in immune memory was impaired. In other words, this study shows that smoking disrupts not only innate immune mechanisms, but also some adaptive immune mechanisms.
A comparison of immune responses in smokers and ex-smokers revealed that the inflammatory response returned to normal levels quickly after smoking cessation, while the impact on adaptive immunity persisted for 10 to 15 years. This is the first time it has been possible to demonstrate the long-term influence of smoking on immune responses.
Darragh DuffyHead of the Translational Immunology Unit at the Institut Pasteur and last author of the study
Basically, the immune system appears to have something resembling a long-term memory of the effects of smoking. But how? "When we realized that the profiles of smokers and ex-smokers were similar, we immediately suspected that epigenetic processes were at play(3)," says Violaine Saint-Andr, a bioinformatician in the Institut Pasteur's Translational Immunology Unit and first author of the study. "We demonstrated that the long-term effects of smoking on immune responses were linked to differences in DNA methylation(4) with the potential to modify the expression of genes involved in immune cell metabolism between smokers, ex-smokers and non-smokers." It therefore appears that smoking can induce persistent changes to the immune system through epigenetic mechanisms.
This is a major discovery elucidating the impact of smoking on healthy individuals' immunity and also, by comparison, on the immunity of individuals suffering from various diseases.
Violaine Saint-AndrBioinformatician in the Institut Pasteur's Translational Immunology Unit and first author of the study
(1) proteins secreted by a large number of immune cells to communicate among themselves and participate in immune defense.
(2) a virus in the herpes family that is often asymptomatic though dangerous to fetuses.
(3) changes in DNA that affect how genes are expressed, i.e. how they are used by cells.
(4) methylation is a type of chemical modification. Methyl groups position themselves on DNA, changing the way in which the genome is read in the cell.
Smoking changes adaptive immunity with persistent effects, Nature, February 14, 2024
Violaine Saint-Andr1,2*, Bruno Charbit3, Anne Biton2, Vincent Rouilly4, Cline Possm1, Anthony Bertrand1,5, Maxime Rotival6, Jacob Bergstedt6,7,8, Etienne Patin6, Matthew L. Albert9, Lluis Quintana-Murci6,10, Darragh Duffy1,3*, and the Milieu Interieur Consortium
1Translational Immunology Unit, Department of Immunology, Institut Pasteur, Universit Paris Cit, Paris 75015, France. 2Bioinformatics and Biostatistics HUB, Department of Computational Biology, InstitutPasteur, Universit Paris Cit, Paris 75015, France. 3Cytometry and Biomarkers UTechS, Center for Translational Research, Institut Pasteur, Universit Paris Cit, Paris 75015, France. 4DATACTIX, Paris, France. 5Frontiers of Innovation in Research and Education PhD Program, LPI Doctoral School, Universit Paris Cit, Paris, France. 6Institut Pasteur, Universit Paris Cit, CNRS UMR2000, Human Evolutionary Genetics Unit, Paris 75015, France. 7Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 8Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 9HIBIO, San Francisco, California, USA. 10Chair Human Genomics and Evolution, Collge de France, Paris 75005, France. *Corresponding author
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Smoking has long-term effects on the immune system - Institut Pasteur