Research: My thesis research focuses on developing safe and effective CD8+ T cell receptor (TCR)-engineered T cell therapies for solid tumors, using murine pancreatic ductal adenocarcinoma (PDA) as a model system. Thus far, I have engineered antigen-specific CD8+ T cells from TCR exchange (TRex) mice to express constitutive cytokine fusion protein (CFP) constructs, which markedly enhance antitumor activity but also cause significant systemic toxicity in orthotopic KPC models. These findings underscore the need for more precise control, and I am now investigating tightly regulated autocrine and paracrine cytokine expression strategies that restrict activity to the tumor microenvironment. By improving T cell functionality and persistence while avoiding the toxicity associated with unregulated cytokine delivery, my goal is to reduce tumor burden, extend survival, and ultimately translate these approaches into primary human T cells.
