On September 4, 2018 Aduro Biotech, Inc. (NASDAQ: ADRO) reported the publication of a peer reviewed paper in Leukemia authored by scientists from the Dana Farber Cancer Institute and Aduro as part of their ongoing collaboration to study the role of APRIL (A PRoliferation Inducing Ligand) in multiple myeloma (MM) (Press release, Aduro Biotech, SEP 4, 2018, View Source;p=RssLanding&cat=news&id=2366001 [SID1234529283]). The authors profile the impact that APRIL, acting through its receptor TACI (transmembrane activator and cyclophilin ligand interactor), has on immune regulatory T cells (Tregs) in MM. The paper further reports that APRIL binding to TACI contributes to the immunosuppressive and treatment resistant MM bone marrow microenvironment, an effect that could potentially be mitigated by anti-APRIL antibody, BION-1301. Aduro is currently advancing BION-1301 in a Phase 1/2 dose escalation trial for the treatment of MM.
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Key findings from the study include the observation that TACI expression is significantly higher in Tregs than conventional T cells from the same patient. APRIL significantly stimulates proliferation and survival of these Tregs, whereas a neutralizing anti-APRIL antibody (BION-1301) may inhibit these effects. Furthermore, the paper explained how APRIL specifically augments Tregs to enhance MM cell survival.
"It is now well-known that APRIL acts through its two receptors TACI and BCMA (B cell maturation antigen), the most specific MM antigen expressed at high levels in malignant plasma cells/B cells of all MM patients. Our newest findings from this study indicate that an anti-APRIL antibody such as BION-1301 may have the potential to treat MM through a differentiated mechanism of action, not only by inhibiting APRIL binding to BCMA, but also stimulating immunity to cancer by blocking APRIL binding to TACI," commented Dr. Yu-Tzu Tai, lead author and Principal Scientist in Medical Oncology at the Dana-Farber Cancer Institute.
The paper entitled "APRIL signaling via TACI mediates immunosuppression by T regulatory cells in multiple myeloma: therapeutic implications," can be accessed at View Source
About APRIL
APRIL is a member of the tumor necrosis factor superfamily and is primarily secreted by bone marrow and/or myeloid cells. APRIL is overproduced in patients with multiple myeloma and binds to BCMA and TACI to stimulate a wide variety of responses that promote MM growth and survival and suppress the immune system so that the tumor cells are protected and sustained in the bone marrow.
About BION-1301
Aduro is currently evaluating BION-1301, its most advanced proprietary B-select monoclonal antibody, as a novel therapy for MM. Despite new treatments recently approved in MM, this disease remains incurable as patients relapse, or become resistant to, currently-available therapies. In preclinical studies, Aduro has established that APRIL plays a crucial part in the protective bone marrow tumor microenvironment. In these studies, APRIL, through BCMA, was shown to be critically involved in the survival, proliferation and chemoresistance of MM, and upregulates mechanisms of immunoresistance, including PD-L1 upregulation. BION-1301, a humanized antibody that blocks APRIL from binding to its receptors, has been shown in preclinical studies to halt tumor growth and overcome drug resistance. In addition, BION-1301 also demonstrated the ability to inhibit immune suppressive effects of regulatory T cells via TACI but not BCMA in MM blood and bone marrow. BION-1301 is currently being evaluated in a Phase 1/2 clinical study in patients with relapsed or refractory MM.