The marine-derived compound trabectedin depletes both human primary leukemic cells and myeloid-derived suppressor cells, according to a new study published in Cancer Immunology Research.1 The researchers think their findings could lead to a new therapy that targets both leukemic cells and the protumor microenvironment, repairing the immune dysfunction that is characteristic of chronic lymphocytic leukemia (CLL).

CLLis characterized by lymphocyte accumulation in the blood, bone marrow, andlymphoid tissues.2 Recent advances in CLL therapy have come fromfinding and targeting the appropriate molecular pathways of the disease,explained Kanti R. Rai, MD, a professor of medicine and molecular medicine atthe Donald and Barbara Zucker School of Medicine at Hofstra/Northwell whowasnt involved in the study. Dr Rai said that, for instance, the Brutontyrosine kinase inhibitor ibrutinib binds to the receptor and affects B-cellreceptorsignaling. Another drug, venetoclax, an antagonist to BCL2, can effectivelyinduce apoptosis in CLL cells. However, treatment of this disease remainschallenging due to its immunosuppressive nature. If we [are] to attain a cure,newer compounds have to be identified which have a different mechanism ofcontrolling CLL, he said.

Patientswith CLL have dysfunctional T cells, noted Maria Teresa Bertilaccio, PhD, whois an assistant professor in the department of experimental therapeutics at TheUniversity of Texas MD Anderson Cancer Center in Houston, and the correspondingauthor of the study. Patients [with CLL] have immunosuppression features, sothey might develop an infection because their immune system is not working,she told Cancer Therapy Advisor. Our approach is not only to eradicateleukemia, but also to rearm the immune system to give patients a better qualityof life.

Trabectedintargets tumor-associated macrophages (TAMs); TAMs are thought to support CLLgrowth. A previous study by the Bertilaccio group showed that depleting TAMs byblocking CSF1R signaling reprograms the tumor microenvironment toward anantitumor phenotype.3 This led them to hypothesize that trabectedincould simultaneously target both leukemic cells and nonmalignant cells in thetumor microenvironment.

Continued here:
Trabectedin Targets Leukemic Cells and Restores Immune Cell Function in Models of Chronic Lymphocytic Leukemia - Cancer Therapy Advisor