11 Sep Humanized Antibody To Attack Resistant Multiple Myeloma Cells in Bone Marrow
MedicalResearch.com Interview with:
Dr. van Eenennaam
Hans van Eenennaam, Ph.D.
Executive vice president antibody research and site head
Aduro Biotech Europe
MedicalResearch.com: What is the background for this study?
Response: A PRoliferation Inducing Ligand (APRIL) is a member of the tumor necrosis factor superfamily and has been shown to stimulate the proliferation and survival of healthy B-lymphocytes. Malignant B-lymphocytes, such as multiple myeloma, use APRIL primarily in the bone marrow to support its proliferation and survival. Studies have shown that APRIL is overproduced in patients with multiple myeloma and mediates primarily via binding to B-cell maturation antigen (BCMA) to stimulate a wide variety of responses that promote multiple myeloma growth and survival, as well as suppressing the immune system so that the tumor cells are protected and sustained in the bone marrow and can escape current available treatments.
MedicalResearch.com: What are the main findings?
Response: The key findings from the study published in Leukemia, authored by scientists from the Dana Farber Cancer Institute and Aduro, include the observation that the second receptor of APRIL, transmembrane activator and cyclophilin ligand interactor (TACI) is significantly higher expressed on Tregs than conventional T cells from the same patient. APRIL significantly stimulates proliferation and survival of these Tregs. Furthermore, the paper explained how APRIL specifically augments Tregs to enhance multiple myeloma cell survival.
MedicalResearch.com: What should readers take away from your report?
Response: The researchers found that APRIL binding to TACI contributes to the immunosuppressive and treatment resistant myeloma bone marrow microenvironment, an effect that could potentially be mitigated by anti-APRIL antibody, such as BION-1301, a humanized antibody that blocks APRIL from binding to its receptors. These TACE-mediated immunomodulatory effects of anti-APRIL sets targeting of multiple myeloma with BION-1301 apart from other BCMA targeting agents.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Based on preclinical studies such as these, Aduro is currently advancing BION-1301 in a Phase 1/2 dose escalation trial for the treatment of multiple myeloma.
MedicalResearch.com: Is there anything else you would like to add?
Response: Despite new treatments recently approved in multiple myeloma, this disease remains incurable as patients relapse, or become resistant to, currently-available therapies. Aduro and its collaborators have established that APRIL plays a crucial role in the protective bone marrow tumor microenvironment that aids and sustains remnant tumor cells to escape current treatments. If successful in clinical studies, BION-1301 could offer a new avenue of treatment to multiple myeloma patients.
Citation:
The paper entitled “APRIL signaling via TACI mediates immunosuppression by T regulatory cells in multiple myeloma: therapeutic implications,” can be accessed at https://www.ncbi.nlm.nih.gov/pubmed/30135465.
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Last Updated on September 11, 2018 by Marie Benz MD FAAD