Grants - Designated Grants - California - 2021

Tannishtha Reya, PhD

Funded in partnership with the Cancer Research Institute through the V Foundation’s Virginia Vine event and Wine Celebration Fund-A-Need

Acute Myelogenous Leukemia (AML) is a cancer that is marked by the uncontrolled growth of immature cells of the myeloid lineage. Current therapies are often not effective, with therapy-resistant cancer cells leading to relapse and death in many patients, including both children and adults. Our goal is to develop a biologic that can block the growth and progression of myeloid leukemias. In previous work, we identified the cell surface protein Tetraspanin3 (Tspan3) as a key new regulator of AML, and showed that its inhibition led to a block in AML growth and improved survival in preclinical models. These data, as well as the successful antibody-mediated targeting of CD20, a tetraspanin-like molecule, provided a strong rationale for developing therapeutic monoclonal antibodies (mAbs) against Tspan3. Importantly, in conjunction with a CRO specializing in antibody development for biotech and pharma, we recently generated mAbs against Tspan3 that block the growth of human leukemia samples in vitro and in preclinical models in vivo. These highly promising data suggest that the antibodies we developed may be effective new therapeutics for targeting myeloid leukemia. To move this work forward towards the clinic, we now propose to determine if biomarkers can be identified to stratify patients for responsiveness to Tspan3 mAbs, develop a response signature to evaluate target engagement, and optimize the antibodies for use in human clinical studies. These studies are important because they have the potential to identify a new class of therapies for cancers that are largely unresponsive to current therapies.