Generation of repetitive element-specific T cells to target ovarian cancer

Abstract The immunosuppressive tumor microenvironment in ovarian cancer (OC) enables these tumors to evade the immune system, resulting late diagnosis and poor therapeutic outcomes for patients. This immunosuppression can be partially reversed with epigenetic inhibitors, which stimulate an immunogenic interferon response OC cells by inducing transcription of repetitive elements (REs). However, therapy alone is not curative clinical trials new treatments that further augment are needed. While REs epigenetically silent terminally differentiated cells, their increased expression implicate genomic as unexplored pool antigens. As also upregulates antigen processing presentation generation T specific over-expressed RE-derived antigens may boost recognition cells. Transducing healthy donor a cell receptor construct recognizes RE ERV-K-Env resulted specificity only when co-cultured B lymphoblastoid derived from same was isolated from. Transduced were autologous systems. previous reports have shown ERV-K-Env-specific expanded patients OC, current studies underway expand Upon successful expansion multiple patients, we will assess if enhanced treating therapy. These efforts serve novel approach enhance improve overall patient survival rate. NIH F31 CA271788-01 DOD W81XWH2010273