Jocelyn Padilla

A major obstacle to the efficacy of cancer immunotherapy is the immunosuppressive tumor microenvironment that promotes T cell dysfunction or exhaustion. My research aims to identify and target new mediators of T cell exhaustion to provide effective treatment options for patients with tumors refractory to currently available immunotherapies.

While immunotherapy is a promising treatment for some patients, not all tumors respond to treatment or those that do respond are at risk of becoming resistant to the therapy. One challenge faced by immunotherapy is the immunosuppressive tumor microenvironment that promotes T cell exhaustion, thereby inhibiting antitumor immunity. Our team has identified specific chemokine interactions that play a role in mediating T cell exhaustion in glioblastoma (GBM) and other cancers. As such, we hypothesized that neutralizing antibodies against these targets can block these immunosuppressive signals thereby enhancing immune responses against GBM and other tumors. We immunized mice with a humanized antibody repertoire to generate antibodies against our chemokine targets and identified 3 top clones which bind and block their targets with sub-nanomolar potency. In vitro co-culture experiments between T cells and ovarian cancer cells showed a robust potentiation of exhausted T cell cytotoxicity when treated with our chemokine-targeted antibody. Successful rescue of T cell cytoxicity in upcoming preclinical models could make chemokine-targeted therapy the next effective treatment option for patients resistant to the current suite of immunotherapies.