In vivo engineering of B7-H3.CAR-T cell therapy for ovarian cancer

Project summary

T cells are immune cells capable of killing specific cells in the body. There is increasing clinical success harnessing T cells to attack cancer, based on modifying a patient s T cells to display chimeric antigen receptor (CAR) that bind unique proteins on cancer cells. Such immune cell therapy, termed CAR-T, is particularly effective in blood cancers. Unfortunately, CAR-T remains a last line therapy, largely due to the time and exorbitant costs to manufacture CAR-T. Current CAR-T is also limited by modest efficacy against solid tumors, likely due to T cell exhaustion from current manufacturing methods. We seek to overcome these shortcomings to enable better CAR-T therapy for ovarian cancer. Specifically, instead of manufacturing CAR-T cells outside the body, we have developed a platform that enables direct engineering of CAR-T cells inside the body (i.e. in vivo), thus greatly reducing the time and costs. By avoiding expansion outside the body, we may also enhance CAR-T activity because CAR-T generated in vivo retain their full potential to expand and persist upon encountering the tumor cells. We have already demonstrated considerable success against aggressive lymphoma and metastatic lung cancer models. In this pilot project, we will perform key proof-of-concept studies demonstrating the feasibility of our approach to generate CAR-T cells that can specifically kill ovarian cancer cells, including in humanized mouse models of ovarian cancer.