The development of humanized SEMA7A-antagonist mAbs for the therapeutic treatment of breast cancer

PROJECT SUMMARY Breast cancer (BC) is the most commonly diagnosed cancer globally and poses significant risk to postpartum women. Targeted therapies have emerged as promising treatment for a variety of cancers and offer a less toxic alternative to traditional treatment strategies, such as chemotherapy. While targeted therapies exist for estrogen receptor positive (ER+) breast cancers, which account for over 70% of cases, ER+ BC is responsible for the majority of BC-related deaths, highlighting the need for improved therapeutic strategies. Furthermore, there are currently no targeted therapies available for the treatment triple-negative breast cancers (TNBC), which are highly aggressive and rely on toxic treatment strategies. Preliminary research has identified Semaphorin 7a (SEMA7A) as a factor associated with decreased survival and treatment resistance in both ER+ and TNBC, leading to increased tumor progression. In response, a novel SEMA7A monoclonal antibody (SmAbH1) was developed, and demonstrates significant potential for slowing tumor progression and diminishing tumor burden in preclinical models. Consequently, PearlSci seeks to further develop and harness SEMA7A-antagonist therapies for BC and potentially other types of cancer. The company's research in this proposal focuses on identifying and validating humanized SEMA7A-antagonist monoclonal antibodies (mAbs) with high binding affinity, characterizing their efficacy in blocking SEMA7A-mediated mechanisms and tumor growth, and assessing their safety and toxicity. Success of the proposed research could lead to more effective treatments for various forms of breast cancer, which will reduce the overall impact on healthcare systems and improve patient outcomes.