Global Immunology Drugs Market to 2022 - Increasing Prevalence, Repositioning Opportunities and Strong Uptake of Interleukin Receptor Inhibitors to Drive Growth

Summary

Immunology is a therapy area characterized by disorders of the immune system, specifically an aberrant autoimmune response against healthy tissues in the body, leading to chronic or acute inflammation. Depending on the specific site affected, this can lead to various types of chronic pain and mobility loss, and have a negative impact on quality of life.

A number of therapies have been approved for immunological disorders, including the largely genericized disease-modifying anti-rheumatic drug (DMARD) class of small molecule drugs. However, as these therapies often fail to elicit an adequate long-term response, a large second-line therapy segment has emerged in these markets, beginning with the approval of Remicade (infliximab) and Enbrel (etanercept) in 1998. There is currently no cure for immunological disorders due to the highly complex nature of the immune system and the fact that many components of the pathophysiological states of these diseases have roles in the healthy immune system.

Autoimmune disorders are currently incurable, and treatment is aimed at managing the disease, in order to reduce the severity of its symptoms and lower the risk of associated co-morbidities. Cytokines and their receptors, such as Tumor Necrosis Factor- and Interleukin-6 are the most effective and most common therapies used in immunology. This class of compounds has been the most commercially successful in the past decade, particularly in the RA market, with many clinical trials underway across various immunological indications. The market for immunological disorders is largely accounted for by premium products, with only a relatively small revenue share accounted for by generics and biosimilars.

Inflectra, a biosimilar of Remicade was recently approved by the FDA in 2016. However, the gradual uptake of biosimilars such as Inflectra is not expected to act as a strong growth driver for the biosimilar segment within the forecast period. This therefore means existing products such as Remicade are expected to maintain high revenues during the forecast period

Although there is a high degree of failure and uncertainty in R&D of immunological drugs, there are 2,054 drugs in active development in the immunology pipeline. In the long-term, this is expected to drive growth in this market in spite of the anticipated approval of biosimilars for key blockbuster drugs and resultant erosion of revenues. Cytokines and their receptors account for the largest single segment of each of the pipelines which make up the largest individual class.

The report focuses on four key indications within immunology: Rheumatoid arthritis, Systemic lupus erythematosus (SLE), Psoriasis and Inflammatory bowel disease (The two major types of Inflammatory bowel disease covered in this report are Ulcerative colitis and Crohns disease). With no curative therapies available, symptomatic medications prescribed off-label are an important part of the treatment paradigm, especially in SLE, increasing the need for extensive R&D within this area.

Scope

- Global revenues for the immunology market are forecast to grow at a compound annual growth rate of 3.63%, from $57.7 billion in 2015 to $74.1 billion in 2022. - Which drugs will achieve blockbuster status and how will the key player companies perform during the forecast period? - The immunological disorders pipeline is large and diverse, and contains 2,054 products. How does the composition of the pipeline compare with that of the existing market? - What molecular targets and molecule types are most commonly being trialed in pipeline products in the key indications? - Which products will contribute to market growth most significantly, and which will achieve blockbuster status? - Will the current market leaders retain their dominance over the forecast period, and how is their revenue share of the immunology market set to change?

Reasons to buy

- Understand the current clinical and commercial landscape by considering disease pathogenesis, diagnosis, prognosis, and the treatment options available at each stage of diagnosis - Visualize the composition of the immunology market across each indication, in terms of dominant molecule types and targets, highlighting the key commercial assets and players - Analyze the immunological disorders pipeline and stratify by stage of development, molecule type and molecular target, with a granular breakdown across key indications - Understand the growth in patient epidemiology and market revenues for the immunology market, globally and across the key players and product types - Stratify the market in terms of the split between generic and premium products, and assess the role of these product types in the treatment of the various immunological disorders. - Identify commercial opportunities in the immunology deals landscape by analyzing trends in licensing and co-development deals

1 Table of Contents 1 Table of Contents 4 1.1 List of Tables 6 1.2 List of Figures 6 2 Introduction 9 2.1 Therapy Area Introduction 9 2.1.1 Rheumatoid Arthritis 9 2.1.2 Systemic Lupus Erythematosus 10 2.1.3 Psoriasis 11 2.1.4 Inflammatory Bowel Disease 12 2.2 Symptoms 13 2.3 Etiology and Pathophysiology 15 2.3.1 Pathophysiology 17 2.4 Epidemiology 21 2.4.1 Rheumatoid Arthritis 22 2.4.2 Systemic Lupus Erythematosus 23 2.4.3 Psoriasis 23 2.4.4 Inflammatory Bowel Disease 24 2.5 Co-morbidities and Complications 25 2.6 Treatment 26 2.6.1 Rheumatoid Arthritis 27 2.6.2 Systemic Lupus Erythematosus 30 2.6.3 Psoriasis 31 2.6.4 Inflammatory Bowel Disease 32 3 Key Marketed Products 34 3.1 Overview 34 3.2 Humira (adalimumab) 34 3.3 Enbrel (etanercept) 36 3.4 Remicade (infliximab) 38 3.5 Rituxan (rituximab) 40 3.6 Stelara (ustekinumab) 42 3.7 Simponi (golimumab) 43 3.8 Prograf (tacrolimus) 45 3.9 Cimzia (certolizumab pegol) 46 3.10 Entyvio (vedolizumab) 47 3.11 Cosentyx (Secukinumab) 49 4 Pipeline Landscape Assessment 51 4.1 Overview 51 4.2 Pipeline Development Landscape 51 4.3 Molecular Targets in the Pipeline 54 4.4 Clinical Trials 56 4.4.1 Failure Rate by Stage of Development, Indication, Molecule Type and Molecular Target 56 4.4.2 Clinical Trial Duration by Stage of Development, Indication, Molecule Type and Molecular Target 60 4.4.3 Clinical Trial Size 65 4.4.4 Aggregate Clinical Program Size 69 4.4.5 Assessment of Key Pipeline Products 72 4.5 Conclusion 80 5 Multi-scenario Market Forecast to 2022 81 5.1 Overall Market Size 81 5.2 Generic Penetration 83 5.3 Revenue Forecast by Molecular Target 84 5.3.1 Tumor Necrosis Factor-Alpha 84 5.3.2 Interleukin Receptor 86 5.3.3 B and T Lymphocyte Antigens 86 5.3.4 Janus Kinases 87 6 Company Analysis and Positioning 89 6.1 Revenue and Market Share Analysis by Company 90 6.1.1 AbbVie Will the Patent Expiration of Humira Cause a Loss in Market Size? 94 6.1.2 Pfizer Xeljanz to Overcome Enbrel Revenue Loss 95 6.1.3 Johnson & Johnson Steady Market Leader over Forecast Period 96 6.1.4 Amgen Will the Patent Expiration of Enbrel Have an Effect on Overall Immunology Revenue? 97 6.1.5 Roche Moderate Revenue Loss Expected due to Biosimilar Competition 98 6.1.6 Eli Lilly Approval of RA Drug to Drive Revenue 99 6.1.7 Bristol-Myers Squibb Will Biosimilar Competition Affect Orencia Revenue? 100 6.1.8 Celgene Otezla and Ozanimod Hydrochloride to Become Blockbuster Drugs 101 6.2 Company Landscape 103 6.3 Marketed and Pipeline Portfolio Analysis 103 7 Strategic Consolidations 106 7.1 Licensing Deals 106 7.1.1 Deals by Region, Year and Value 106 7.1.2 Deals by Stage of Development and Value 108 7.1.3 Deals by Molecule Type, Mechanism of Action and Value 109 7.1.4 Licensing Deals Valued over $100m 111 7.2 Co-development Deals 115 7.2.1 Deals by Region, Year and Value 116 7.2.2 Deals by Stage of Development and Value 117 7.2.3 Deals by Molecule Type, Mechanism of Action and Value 118 7.2.4 Co-development Deals Valued over $100m 120 8 Appendix 124 8.1 References 124 8.2 Table of All Clinical Stage Pipeline Products 132 8.3 Abbreviations 136 8.4 Disease List 137 8.5 Methodology 138 8.5.1 Coverage 138 8.5.2 Secondary Research 138 8.5.3 Market Size and Revenue Forecasts 138 8.5.4 Pipeline Analysis 139 8.5.5 Competitive Landscape 139 8.6 Contact Us 139 8.7 Disclaimer 140

1.1 List of Tables Table 1: Immunology Therapeutics Market, Symptoms of RA, SLE, Psoriasis and IBD 14 Table 2: Immunology Therapeutics Market, Etiology of RA, SLE, Psoriasis and IBD 16 Table 3: Immunology, Global, Epidemiology of Inflammatory Immunological Disorders, 2017 22 Table 4: Immunology Therapeutics Market, Global, Approved Indications for Humira, 2017 35 Table 5: Immunology Therapeutics Market, Global, Approved Indications for Enbrel, 2017 37 Table 6: Immunology Therapeutics Market, Global, Approved Indications for Remicade, 2017 39 Table 7: Immunology Therapeutics Market, Global, Approved Indications for Rituxan, 2017 41 Table 8: Immunology Therapeutics Market, Global, Approved Indications for Stelara, 2017 43 Table 9: Immunology Therapeutics Market, Global, Approved Indications for Simponi, 2017 44 Table 10: Immunology Therapeutics Market, Global, Approved Indications for Prograf, 2017 45 Table 11: Immunology Therapeutics Market, Global, Approved Indications for Cimzia, 2017 46 Table 12: Immunology Therapeutics Market, Global, Approved Indications for Entyvio, 2017 48 Table 13: Immunology Therapeutics Market, Global, Approved Indications for Cosentyx, 2017 50 Table 14: Immunology, Global, Annual Revenue Forecast for Key Products ($m), 20152022 82 Table 15: Immunology, Global, Usage of Generics Across Key Indications, 2017 84 Table 16: Immunology Therapeutics Market, Global, Forecast Revenues by Company, 20152022 91 Table 17: Immunology Therapeutics Market, Global, Licensing Deals Valued over $100m, 20062016 111 Table 18: Immunology Therapeutics Market, Global, Co-development Deals Valued over $100m, 20062017 120

1.2 List of Figures Figure 1: Immunology, Global, Epidemiology Patterns for Rheumatoid Arthritis (000), 20162023 22 Figure 2: Immunology, Global, Epidemiology Patterns for Systemic Lupus Erythematosus (000), 20162023 23 Figure 3: Immunology, Global, Epidemiology Patterns for Psoriasis (000), 20162023 24 Figure 4: Immunology, Global, Epidemiology Patterns for Inflammatory Bowel Disease (000), 20162023 25 Figure 5: Immunology, Global, Key Marketed Products and Approved Indications, 2016 34 Figure 6: Immunology Therapeutics Market, Global, Annual Revenues for Humira ($bn), 20062022 36 Figure 7: Immunology Therapeutics Market, Global, Annual Revenues for Enbrel ($bn), 20062022 38 Figure 8: Immunology Therapeutics Market, Global, Annual Revenues for Remicade ($bn), 20062022 40 Figure 9: Immunology Therapeutics Market, Global, Annual Revenues for Enbrel ($bn), 20062022 42 Figure 10: Immunology Therapeutics Market, Global, Annual Revenues for Stelara ($bn), 20062022 43 Figure 11: Immunology Therapeutics Market, Global, Annual Revenues for Simponi ($bn), 20062022 44 Figure 12: Immunology Therapeutics Market, Global, Annual Revenues for Prograf ($bn), 20062022 46 Figure 13: Immunology Therapeutics Market, Global, Annual Revenues for Cimzia ($bn), 20062022 47 Figure 14: Immunology Therapeutics Market, Global, Annual Revenues for Entyvio ($bn), 20062022 49 Figure 15: Immunology Therapeutics Market, Global, Annual Revenues for Cosentyx ($bn), 20062022 50 Figure 16: Antibacterial Drug Market, Global, Overall Pharmaceutical Industry Pipeline by Therapy Area, 2017 51 Figure 17: Immunology Therapeutics Market, Global, Pipeline for Immunology by Stage of Development, Molecule Type and Program Type, 2017 52 Figure 18: Immunology Therapeutics Market, Global, Pipeline for Key Immunology Indications by Stage of Development, 2017 53 Figure 19: Immunology Therapeutics Market, Global, Pipeline for Key Immunology Indications by Molecule Type, 2017 54 Figure 20: Immunology Therapeutics Market, Pipeline by Mechanism of Action (%), 2017 55 Figure 21: Immunology Therapeutics Market, Global, Pipeline for Key Immunology Indications by Molecular Target, 2017 56 Figure 22: Immunology Therapeutics Market, Global, Clinical Trial Attrition Rates by Stage of Development (%), 20062017 57 Figure 23: Immunology Therapeutics Market, Global, Clinical Trial Attrition Rates by Stage of Development and Indication (%), 20062017 58 Figure 24: Immunology Therapeutics Market, Global, Clinical Trial Attrition Rates by Stage of Development and Molecule Type (%), 20062017 59 Figure 25: Immunology Therapeutics Market, Global, Clinical Trial Attrition Rates by Stage of Development and Molecular Target (%), 20062017 60 Figure 26: Immunology Therapeutics Market, Global, Clinical Trial Duration by Stage of Development (months), 20062017 61 Figure 27: Immunology Therapeutics Market, Global, Clinical Trial Duration by Stage of Development and Indication (months), 20062017 62 Figure 28: Immunology Therapeutics Market, Global, Clinical Trial Duration by Stage of Development and Molecule Type (months), 20062017 63 Figure 29: Immunology Therapeutics Market, Global, Clinical Trial Duration by Stage of Development and Molecular Target (months), 20062017 64 Figure 30: Immunology Therapeutics Market, Global, Clinical Trial Size by Stage of Development (patients), 20062017 65 Figure 31: Immunology Therapeutics Market, Global, Clinical Trial Size by Stage of Development and Indication (participants), 20062017 66 Figure 32: Immunology Therapeutics Market, Global, Clinical Trial Size by Stage of Development and Molecule Type (participants), 20062017 67 Figure 33: Immunology Therapeutics Market, Global, Clinical Trial Size by Stage of Development and Molecular Target (participants), 20062017 68 Figure 34: Immunology Therapeutics Market, Global, Clinical Program Size by Stage of Development (months), 20062017 69 Figure 35: Immunology Therapeutics Market, Global, Clinical Program Size by Stage of Development and Indication (participants), 20062017 70 Figure 36: Immunology Therapeutics Market, Global, Clinical Program Size by Stage of Development and Molecule Type (participants), 20062017 71 Figure 37: Immunology Therapeutics Market, Global, Clinical Program Size by Stage of Development and Molecular Target (participants), 20062017 72 Figure 38: Immunology Therapeutics Market, Global, Revenue Forecast for sarilumab ($bn), 20162022 74 Figure 39: Immunology Therapeutics Market, Global, Revenue Forecast for sirukumab ($m), 20152022 75 Figure 40: Immunology, Global, Annual Revenue Forecast for baricitinib ($bn), 20152022 77 Figure 41: Immunology, Global, Annual Revenue Forecast for upadacitinib ($m), 20152022 78 Figure 42: Immunology, Global, Annual Revenue Forecast for ozanimod ($bn), 20192022 79 Figure 43: Immunology, Global, Market Size ($m), 20152022 81 Figure 44: Immunology, Global, Annual Revenue Forecast for Key Products ($m), 20152022 83 Figure 45: Immunology, Global, Annual Revenue Forecast for Tumor Necrosis Factor-Alpha Inhibitors ($bn), 20152022 85 Figure 46: Immunology, Global, Annual Revenue Forecast for Interleukin Inhibitors ($bn), 20152022 86 Figure 47: Immunology, Global, Annual Revenue Forecast for B and T Lymphocyte Antigens ($bn), 20152022 87 Figure 48: Immunology, Global, Annual Revenue Forecast for Janus Kinases ($bn), 20152022 88 Figure 49: Immunology Therapeutics Market, Global, Cluster by Growth and Market Share, 20152022 89 Figure 50: Immunology Therapeutics Market, Global, Forecast Market Share by Company (%), 20152022 92 Figure 51: Immunology, Global, Companies by Compound Annual Growth Rate (%), 20142022 93 Figure 52: Immunology, Global, Revenues by Product Type, 20152022 94 Figure 53: Immunology, Global, AbbVie Annual Revenue Forecast ($bn), 20152022 95 Figure 54: Immunology, Global, Pfizer Annual Revenue Forecast ($bn), 20152022 96 Figure 55: Immunology, Global, Johnson & Johnson Annual Revenue Forecast ($bn), 20152022 97 Figure 56: Immunology, Global, Amgen Annual Revenue Forecast ($bn), 20152022 98 Figure 57: Immunology, Global, Roche Annual Revenue Forecast ($bn), 20152022 99 Figure 58: Immunology, Global, Eli Lilly Annual Revenue Forecast ($bn), 20152022 100 Figure 59: Immunology, Global, Bristol-Myers Squib Annual Revenue Forecast ($bn), 20152022 101 Figure 60: Immunology, Global, Celgene Annual Revenue Forecast ($bn), 20152022 102 Figure 61: Immunology, Global, Companies by Type, 2017 103 Figure 62: Immunology, Global, High-Activity and Late-Stage Pipeline Developers by Level of immunology specialization, 2017 104 Figure 63: Immunology, Global, Proportion of Company Revenue Attributed to immunology, 20152022 105 Figure 64: Immunology, Global, Licensing Deals, 20062017 107 Figure 65: Immunology, Global, Licensing Deals by Indication and Value, 20062017 108 Figure 66: Immunology, Global, Licensing Deals, 20062017 109 Figure 67: Immunology, Global, Licensing Deals by Molecule Type and Mechanism of Action, 20062017 110 Figure 68: Immunology, Global, Co-development Deals, 20062017 116 Figure 69: Immunology, Global, Co-development Deals by Indication and Value, 20062017 117 Figure 70: Immunology, Global, Co-development Deals, 20062017 118 Figure 71: Immunology, Global, Co-development Deals by Molecule Type and Mechanism of Action, 20062017 119 Figure 72: Immunology, Global, Table of all Clinical Stage Pipeline Products, Part I, 2017 132 Figure 73: Immunology, Global, Table of all Clinical Stage Pipeline Products, Part II, 2017 133 Figure 74: Immunology, Global, Table of all Clinical Stage Pipeline Products, Part III, 2017 134 Figure 75: Immunology, Global, Table of all Clinical Stage Pipeline Products, Part IV, 2017 135

Link:
Global Immunology Drugs Market to 2022 - Increasing ...

Once the libraries are sequenced, it is possible to pair the alpha and beta sequences from each individual cell. The 10x Genomics Cell Ranger bioinformatics pipeline assembles V(D)J short sequence reads into consensus alpha and beta chain annotated full-length paired V(D)J profiles.

The Cell Ranger pipeline filters the reads based on shared homology with germline V, D, J, constant segments and assembles the filtered reads within each barcode producing contigs, then annotates the contig sequences with the best germline V, D, J, constant, and UTR matches, detecting and translating the CDR3 sequence. It then groups cells into clonotypes, which share all productive CDR3 sequences, building a consensus for each chain in each clonotype.

To validate the Chromium Single Cell V(D)J Solution performance, the product was used to profile a variety of samples containing T cells. In one experiment, two samples of peripheral blood mononuclear cells (PBMCs) from the same healthy individual were sequenced to confirm that the two independently run samples would exhibit similar behavior. Since the samples came from a healthy individual with no known challenges to the immune system, researchers expected to see high T-cell diversity and low antigen specificity.

Cell Ranger software grouped the T cells into clonotypes and calculated the percent that each clonotype was represented in the sample. In the first sample, 2,809 clonotypes were detected, and 2,949 were detected in the second sample. As expected, no clonotype made up >0.5% of either sample, demonstrating a very high diversity and low specificity in the sample.

To determine antigen specificity, an experiment was performed using T cells exposed to the Epstein-Barr Virus (EBV) in cell culture (Figure 3). The EBV-specific T cells captured and sequenced by the Chromium System were sorted into clonotypes. It was found that 55% of the sequenced T cells shared one major alpha and beta chain, TRAV12-3:J20 (CDR3: CATQGSNDYKLSF), TRBV9:D1:J1-4 (CDR3: CASSTGQVATNEKLFF); 9% shared a second, unrelated clonotype, TRAV5:J15, TRBV14:D2:J2-1; 4% had two related clonotypes that shared a common beta chain3% with TRAV5:J15, TRBV29-1:D1:J1-4 and 1% with TRAV5:J23, TRBV29-1:D1:J1-4.

After the antigen specificities and frequencies of each of the four most dominant clonotypes were determined, limit-of-detection (LOD) experiments were performed using 1:99 dilutions of the EBV-specific T cells mixed into replicate samples of PBMCs from a healthy donor (Figure 3).

In this experiment, one would expect the most dominant clonotype (55%) from the EBV-specific T cells to be observed at a frequency of 0.55% when spiked into the PBMC background. Consistent with these expectations, 16 cells (0.4%) and 7 cells (0.3%) were found to express the major EBV-specific clonotype (TRAV12-3:J20, TRBV9:D1:J1-4) in the first and second spike-in replicates, respectively.

Interestingly, the Chromium V(D)J Solution was able to detect two cells (0.05%) and one cell (0.05%), respectively, of the second most abundant EBV-specific clonotype, resulting in an LOD of <0.1%. This limit of detection is likely to be pushed even lower as future experiments using more input T cells and greater sequencing depths enable the detection of even more rare known clonotypes.

The V(D)J Solution supports diverse basic and translational research studies of applied immunology and will ultimately accelerate our understanding of human health and disease. Particularly exciting application areas that will be propelled by the V(D)J Solution include T cellbased immunotherapies and with the addition of a planned B-cell-specific VDJ solution, vaccine development.

The V(D)J Solution will do this by enabling the identification of the true paired diversity of antigen receptors on a single-cell basis and thereby more effectively enable functional studies into the molecular genetic determinants of antigen specificity.

When coupled with assessments of immune repertoire diversity across experimental contexts of normal healthy tissues, longitudinal or case/control studies, and shared immune responses to common exposure histories, the V(D)J Solution will elucidate the adaptive immune system with greater resolution than ever before

Read more:
High-Definition Immunology - Genetic Engineering & Biotechnology News

non-specific immune system with a rapid reaction time to keep

skin, mucous membranes, stomach acid, sweat, etc. ... -epithelial

functional barrier where cilia sweeps mucus and secretes antim

secretes mucus, traps microbes, and prevents adhesion. (part o

Innate Immune System

non-specific immune system with a rapid reaction time to keep

1st line of defense in non-specific def

skin, mucous membranes, stomach acid, sweat, etc. ... -epithelial

Continue reading here:
Search immunology | Quizlet

Immunology is a branch of biomedical sciences that deals with the study of the physiology, molecular biology and genetics of the immune system and its componentsduring the state of wellbeing as well as illness. It studies and implies the physiological, chemical, physical characteristic features of the system towards comprehending the underlying pathophysiology of diseased conditions and developing suitable treatment practices. Immunological research involves study of the structure and function of Thymus, bone marrow, spleen, tonsil, lymph vessels, lymph nodes, adenoids, skin and liver. Classical Immunology is intricately tied with epidemiology and medicine and helps in the study of the relationship between the body system and pathogens, and the role of immune system in safeguarding the body from such attacks.

Read more:
Immunology Journals Journals - OMICS International

The 2017Warren Alpert Foundation Prizehas been awarded to five scientists for transformative discoveries in the field of cancer immunology.

Collectively, their work has elucidated foundational mechanisms in cancers ability to evade immune recognition and, in doing so, has profoundly altered the understanding of disease development and treatment. Their discoveries have led to the development of effective immune therapies for several types of cancer.

The 2017 award recipients are:

The honorees will share a $500,000 prize and will be recognized at a day-long symposium on Oct. 5 at Harvard Medical School.

The Warren Alpert Foundation, in association with Harvard Medical School, honors trailblazing scientists whose work has led to the understanding, prevention, treatment or cure of human disease. The award recognizes seminal discoveries that hold the promise to change our understanding of disease or our ability to treat it.

The discoveries honored by the Warren Alpert Foundation over the years are remarkable in their scope and potential, said George Q. Daley, dean of Harvard Medical School. The work of this years recipients is nothing short of breathtaking in its profoundimpacton medicine. These discoveries have reshaped our understanding of the bodys response to cancer and propelled our ability to treat several forms of this recalcitrant disease.

The Warren Alpert Foundation Prize is given internationally. To date, the foundation has awarded nearly $4 million to 59 scientists. Since the awards inception, eight honorees have also received a Nobel Prize.

Wecommend these five scientists.Allison, Chen, Freeman,Honjoand Sharpe are indisputable standouts in the field ofcancer immunology, said Bevin Kaplan, director of the Warren Alpert Foundation. Collectively,they are helping to turn the tide in the global fight against cancer. We couldn'thonor more worthy recipients for the Warren Alpert Foundation Prize.

The 2017 award: Unraveling the mysterious interplay between cancer and immunity

Understanding how tumor cells sabotage the bodys immune defenses stems from the collective work of many scientists over many years and across multiple institutions.

Each of the five honorees identified key pieces of the puzzle.

The notion that cancer and immunity are closely connected and that a persons immune defenses can be turned against cancer is at least a century old. However, the definitive proof and demonstration of the steps in this process were outlined through findings made by the five 2017 Warren Alpert prize recipients.

Under normal conditions, so-called checkpoint inhibitor molecules rein in the immune system to ensure that it does not attack the bodys own cells, tissues and organs. Building on each others work, the five award recipients demonstrated how this normal self-defense mechanism can be hijacked by tumors as a way to evade immune surveillance and dodge an attack. Subverting this mechanism allows cancer cells to survive and thrive.

A foundational discovery made in the 1980s elucidated the role of a molecule on the surface of T cells, the bodys elite assassins trained to seek, spot and destroy invaders.

A protein called CTLA-4 emerged as a key regulator of T cell behaviorone that signals to T cells the need to retreat from an attack. Experiments in mice lacking CTLA-4 and use of CTLA-4 antibodies demonstrated that absence of CTLA-4 or blocking its activity could lead to T cell activation and tumor destruction.

Subsequent work identified a different protein on the surface of T cellsPD-1as another key regulator of T cell response. Mice lacking this protein developed an autoimmune disease as a result of aberrant T cell activity and over-inflammation.

Later on, scientists identified a molecule, B7-H1, subsequently renamed PD-L1, which binds to PD-1, clicking like a key in a lock. This was followed by the discovery of a second partner for PD-1the molecule PD-L2which also appeared to tame T-cell activity by binding to PD-1.

The identification of these molecules led to a set of studies showing that their presence on human and mouse tumors rendered the tumors resistant to immune eradication.

A series of experiments further elucidated just how tumors exploit the interaction between PD-1 and PD-L1 to survive. Specifically, some tumor cells appeared to express PD-L1, essentially wrapping themselves in it to avoid immune recognition and destruction.

Additional work demonstrated that using antibodies to block this interaction disarmed the tumors, rendering them vulnerable to immune destruction.

Collectively, the five scientists findings laid the foundation for antibody-based therapies that modulate the function of these molecules as a way to unleash the immune system against cancer cells.

Antibody therapy that targets CTLA-4 is currently approved by the FDA for the treatment of melanoma. PD-1/PD-L1 inhibitors have already shown efficacy in a broad range of cancers and have been approved by the FDA for the treatment of melanoma; kidney; lung; head and neck cancer; bladder cancer; some forms of colorectal cancer; Hodgkin lymphoma and Merkel cell carcinoma.

In their own words

"I am humbled to be included among the illustrious scientists who have been honored by the Warren Alpert Foundation for their contributions to the treatment and cure of human disease in its 30+ year history.It is also recognition of the many investigators who have labored for decades to realize the promise of the immune system in treating cancer. -James Allison

The award is a great honor and a wonderful recognition of our work. -LiepingChen

I am thrilled to have made a difference in the lives of cancer patients and to be recognized by fellow scientists for my part in the discovery of the PD-1/PD-L1 and PD-L2 pathway and its role in tumor immune evasion. I am deeply honored to be a recipient of the Alpert Award and to be recognized for my part in the work that has led to effective cancer immunotherapy. The success of immunotherapy has unleashed the energies of a multitude of scientists to further advance this novel strategy. -Gordon Freeman

Iam extremely honored to receive the Warren Alpert Foundation Prize.I am very happy that our discovery of PD-1 in 1992 and subsequent 10-year basic research on PD-1 led to its clinical application as a novel cancer immunotherapy. I hope this development will encourage many scientists working in the basic biomedical field. -TasukuHonjo

I am truly honored to be a recipient of the Alpert Award. It is especially meaningful to be recognized by my colleagues for discoveries that helped define the biology of the CTLA-4 and PD-1 pathways. The clinical translation of our fundamental understanding of these pathways illustrates the value of basic science research, and I hope this inspires other scientists. -Arlene Sharpe

Previous winners

Last years awardwent to five scientists who were instrumental in the discovery and development of the CRISPR bacterial defense mechanism as a tool for gene editing. They wereRodolpheBarrangouof North Carolina State University,Philippe Horvathof DuPont inDang-Saint-Romain, France,JenniferDoudnaof the University of California, Berkeley,EmmanuelleCharpentierof the Max Planck Institute for Infection Biology in Berlin andUmeUniversity in Sweden, andVirginijusSiksnysof the Institute of Biotechnology at Vilnius University in Lithuania.

Other past recipients include:

The Warren Alpert Foundation

Each year theWarren Alpert Foundationreceives between 30 and 50 nominations from scientific leaders worldwide. Prize recipients are selected by the foundations scientific advisory board, which is composed of distinguished biomedical scientists and chaired by the dean of Harvard Medical School.

Warren Alpert (1920-2007), a native of Chelsea, Mass., established the prize in 1987 after reading about the development of a vaccine for hepatitis B. Alpert decided on the spot that he would like to reward such breakthroughs, so he picked up the phone and told the vaccines creator, Kenneth Murray of the University of Edinburgh, that he had won a prize. Alpert then set about creating the foundation.

To award subsequent prizes, Alpert asked DanielTosteson(1925-2009), then dean of Harvard Medical School, to convene a panel of experts to identify scientists from around the world whose research has had a direct impact on the treatment of disease.

Read the rest here:
Warren Alpert Foundation Honors Five Pioneers in Cancer Immunology - Harvard Medical School (registration)

As the nearly 800 currently ongoing studies involving anti-PD-(NYSE:L)1 agents combined with other approaches speed towards readout investors will be faced with a tough question: how precisely to interpret the overwhelming amount of data generated.

The issue took centre stage at a panel discussion at today's Sachs Associates Immuno-oncology Forum on the sidelines of the Asco meeting. It will be one of several things the industry will grapple with, though it is by now abundantly clear that there is no stopping the combo study runaway train.

That fact was illustrated in a report just published by EP Vantage, which showed that the absolute number of anti-PD-(L)1 combo trials under way - with numerous mechanistic approaches - had surged nearly fourfold since November 2015 to reach 765 in April.

Dr James Mul, from the Moffitt Cancer Center, told the Sachs conference that it was hard to imagine just how rapidly these trials were being conducted. In terms of subjects enrolled, he cited data showing that there were now over 250,000 patients in active immuno-oncology studies.

"But there will be no clear-cut direction as to where combo studies are heading until about 2019," he said. "There's still a way to go before we can make clear-cut decisions."

John Beadle, chief executive of Psioxus, whose oncolytic virus enadenotucirev is being combined with Bristol-Myers Squibb's (NYSE:BMY) Opdivo, called the expected surge of data an "exponential avalanche of information".

Still, most of these studies are too early to involve randomisation, and many are not designed to answer the simple, head-to-head question of whether A plus B is better than A or B alone. And, while it is clear than many combos will not work, what yardsticks should investors use to determine whether a combination has actually given an incremental benefit?

The panel suggested that one aspect of particular relevance should be to look at whether a study involves subjects who have already failed on a checkpoint inhibitor, or those who have shown resistance to immuno-oncology in general. Signs of efficacy in these patients would clearly be of interest.

IO-IO or back to basics?

Paul Rennert, chief executive of Aleta Biotherapeutics, who was co-chairing the panel with Dr. Mul, drilled down into the changing expectations behind the various checkpoint combination approaches.

He admitted to having been one of the people who two or three years ago had made much of the potential of combining immuno-oncology with immuno-oncology, assuming that novel targets like Ox40, GITR, Tim3, Vista and others were going to raise immune responses strongly and usher in a new wave of post-PD-(L)1 agents.

"We thought we were going to get response rates up. We're not seeing that yet," he admitted. "Perhaps it's too early."

On the other hand, perhaps it is checkpoint inhibitor combinations with more traditional approaches, such as small molecules or even simple chemotherapy, that investors should pay attention to. The surge in chemo combo studies was another key finding of the EP Vantage report.

This issue could feed into other important areas such as pharmacoeconomics: a chemo combo approach would clearly be cheaper than one combining two IO agents.

At a separate Sachs Forum discussion focused on deal-making, Timothy Herpin, head of UK transactions at Astrazeneca (NYSE:AZN), said there would likely be continued interest in non-IO mechanisms, but that these would play out in combination with an IO backbone.

Guillaume Vignin, head of IO licensing at Merck KGaA (OTCPK:MKGAF) (OTCPK:MKGAY) said it was too early to call the non-IO combo approach a trend. "But there are exciting data to be published," he said. "The two will be working together - it will not all be about IO-IO."

If one thing is certain, however, it is that data will come thick and fast, and this will affect the way deals are done. The important thing seems to be just to get deals signed to get the combos into the clinic, and generate data, as quickly as possible, said Mr. Herpin.

"Once you have data we can work through the [deal] complexity," he added.

Editor's Note: This article discusses one or more securities that do not trade on a major U.S. exchange. Please be aware of the risks associated with these stocks.

More here:
Deciphering The Immunology Combo Avalanche - Seeking Alpha

Our apologies. An error occurred while setting your user cookie. Please set your browser to accept cookies to continue.

NEJM.org uses cookies to improve performance by remembering your session ID when you navigate from page to page. This cookie stores just a session ID; no other information is captured. Accepting the NEJM cookie is necessary to use the website.

1-800-843-6356 | nejmcust@mms.org

See the rest here:
Allergy/Immunology articles: The New England Journal of ...

The Annual Meeting of the American Association of Immunologists (AAI) is one of the largest annual gatherings of immunologists worldwide. This years meeting, IMMUNOLOGY 2017, held in Washington, DC, USA, saw immunologists from around the world discussing breakthroughs across the full spectrum of topics in the field, while exhibitors displayed the latest technologies for cutting edge techniques.

During the event, MilliporeSigma, a business of Merck KGaA Darmstadt, Germany, presented a range of new solutions for immunologists, including a series of T Cell multiplex assay kits for low-level cytokine detection in small samples volumes, and the CellASIC ONIX2 Microfluidics System for real-time control and manipulation of cellular environment for live cell analysis. Watch the video interviews and presentation to learn more about these innovations and how they can help to advance your immunology research.

New High-Sensitivity Immunoassays Panels Detect Picogram Level Cytokines

Robert Keith, R&D Scientist, MilliporeSigma, introduces three high-sensitivity MILLIPLEX MAP panels to help researchers detect low levels of multiple cytokines in small amounts of sample: the Human High Sensitivity T Cell Magnetic Bead Panel (in both 96-well format and a new 384-well format) and the new Mouse High Sensitivity T Cell Magnetic Bead Panel in 96-well format. Both the human and mouse high-sensitivity panels can detect picogram levels of cytokines in just 25 L of sample for up to 21 or 18 critical cytokines, respectively.

Robert Keith introduces three new high-sensitivity MILLIPLEX MAP panel

Robert Keith highlights the benefits of the new T Cell multiplex assays for immunologists

Automated Cell Culture for Dynamic Analysis of Cell Function in Real Time

Dr Amedeo Cappione, Senior Scientist, MilliporeSigma, explains how the microfluidics-based CellASIC ONIX2 System offers precise real-time control of media perfusion for cell researchers who need a highly controllable and manipulatable cellular environment and the ability to conduct semi-automated, repeatable long-term experiments while continuously collecting quantitative image-based data.

Dr Amedeo Cappione explains how the CellASIC ONIX2 System works

Excerpt from:
Immunoassay and Live Cell Analysis Solutions Presented at IMMUNOLOGY 2017 - SelectScience

BMC Immunology is delighted to announce the launch of a new thematic series: "Cancer Immunotherapy and Vaccines". Here, Guest Editor Francesco Pappalardo gives an introduction to the series and discusses the progress and the difficulties faced by researchers in the field.

Professor Francesco Pappalardo 31 May 2017

Pixabay

Vaccines are the most effective and cost-efficient weapons that can be used to prevent (preventive vaccines) or cure (therapeutic vaccines) diseases caused by infectious agents or cancer cells. Usually, when one thinks about the word vaccine, the first thought that comes into the mind is related to an artificial administration of a stimulus that instructs the immune system to fight against the cause of a particular pathological state (the pathogen). However, in the case of cancer vaccines, the main view, still unknown to the majority of the people not working in the field, is represented by the exploitation of the hosts immune system to treat or prevent cancer. The idea, however, dates back decades.

In the same way a traditional vaccine works, a cancer vaccine can promote the eradication of malignant cells during their initial transformation from safe to harmful cells. This eradication process, commonly referred to as immune surveillance of tumors [1], is carried out by the immune system and, most of the time, it happens without any external intervention. Tumors are the result of a particular combination of factors related to genetic and epigenetic changes that enable immortality.

In the same way a traditional vaccine works, a cancer vaccine can promote the eradication of malignant cells during their initial transformation from safe to harmful cells.

This is not a completely undetectable process: during the transformation of a normal cell into a malignant one, foreign antigens (neo-antigens or, to be more specific, onco-antigens) are created; these should render neoplastic cells visible by the immune system that can target them for elimination. Tumors cells, like every living organisms, want, nevertheless, to live. Hence, tumors try to become resistant and invisible to immune system attacks by developing multiple resistance mechanisms that include local immune evasion, induction of tolerance and systemic interference of T cell signaling. Besides, mimicking the metaphor of Darwins natural selection, immune recognition of cancer cells enforces a selective pressure on developing ones. This favors the development of less immunogenic and more apoptosis-resistant neoplastic cells, through a mechanism well known as immune editing [2].

Due to the fact that cancer cells are particularly good at evading any action from the immune system, most anti-cancer treatments are based on other means like surgery, radiation therapy, and chemotherapy. Nowadays, however, it is clear that the various arms of the immune system play an essential role in protecting humans from cancer. After unsatisfactory efforts and explicit clinical failures, the field of cancer immunotherapy has received a significant boost, thanks mainlyto the development in 2010of an autologous cellular immunotherapy, sipuleucel-T, for the treatment of prostate cancer [3] and the approval of the anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) antibody ipilimumab (2011) andanti-programmed cell death protein 1 (PD1) antibodies (2014) for the treatment of melanoma [4]. These achievements haverenovated the field and brought attention to the opportunities that immunotherapeutic approaches can offer [5,6].

The field of cancer immunotherapy has recently received a significant boost

Pixabay

There are still, however, some difficulties to be overcome when developing effective immunotherapy strategies against cancer. The general lack of understanding of the mechanisms of immunization, the role of dendritic cells, the ability of cancer to induce tolerance, and the identification of the most suitable antigens to use are just some examples of how the development of effective strategies is still problematic [7-10]. There are several biotechnological methodologies, based on both in silico and in vivo techniques, that study and suggest possible candidates for use in immunotherapies. However, they are not able, on their own, to quantify and analyze the immune system response globally. Moreover, there are now several computational techniques to predict T cell epitopes (and,to some extent, also B cell epitopes) [11,12]. Computational simulations may help in solving these issues, but these need to be integrated with the in vitro and in silico molecular analyses [13,14]. So, a complete computational/biological pipeline that allow the best integration of in silico, in vitro and in vivo methodologies may potentially boost and improve cancer immunotherapy development and effectiveness.

The aim of the thematic series is to bring together the latest advances in both biological and computational research, looking broadly at the basic biological aspects of immunotherapy, emerging immunotherapies (both prophylactic and preventive) and different vaccination approaches. The novel, and, at the same time, established character of computation in immunology greatly improves and speeds-up the development of novel vaccination strategies, both therapeutic and preventive, against cancer. We welcome original research, methodology, software, and database article submissions.

The deadline for submission of manuscripts is 30thNovember2017. For more information, visit the BMC Immunology website.

References

View the latest posts on the BMC Series blog homepage

By commenting, youre agreeing to follow our community guidelines.

Go here to see the original:
New Thematic Series for BMC Immunology: Cancer Immunotherapy ... - BMC Blogs Network (blog)

Dr. Iram Sirajuddin will bring a new specialty to Susan B. Allen Memorial Hospital. She is an Allergist and Immunologist, who will see patients in the SBA Clinic Augusta beginning Monday, June 5.

Dr. Sirajuddin got interested in medicine at a young age. Her father is a doctor (anesthesiologist) and she enjoyed hearing him discuss his cases with the family. She also had a cousin with a blood disorder and would sometimes accompany her to doctors appointments. She was inspired by the caring relationship between the doctor and her cousin.

Thats what drew me to medicine, Dr. Sirajuddin said.

Dr. Sirajuddin attended medical school at the 6-year program at the University of Missouri - Kansas City. She trained at St. Louis Childrens Hospital with Washington University. Her residency was in Pediatrics.

I have always loved working with children, she said. Their energy and curiosity about things is something I admire.

She rotated through different specialties during her training, and developed an interest in Allergy/Immunology.

I feel when I do my job correctly, it can help people lead their best possible lives, Dr. Sirajuddin said. Its a field where you can say you really have made a difference.

She is trained to see adults and children with seasonal and food allergies, asthma, eczema and immunodeficiencies.

She moved to Wichita in 2010 and worked for the KU Medical Center from 2010 to 2012. She took an extended maternity leave, then returned to work doing Telemedicine in 2015.

She said the Telemedicine company she worked for was focused on rural Kansas and providing services to people who didnt have easy access to the medical care they needed.

While Dr. Sirajuddin enjoyed this, she said she missed the face-to- face contact with patients.

I love seeing patients face to face and building that relationship with them in person, she said.

That made her start thinking about getting back into an office setting.

While she worked at KU, she had come to SBAMH to introduce herself to the pediatricians because she was only seeing pediatric patients at the time.

She said when she recently started looking at job opportunities, she recalled how those doctors were good to work with and seemed happy where they worked.

Read this article:
Dr. Sirajuddin to offer allergy, immunology services at SBAMH - Butler County Times Gazette