California's Stem Cell Agency

Research Objective

We are developing a tumor-associated glycan-targeting CAR T cell with inducible cytokine production that drives T cell stem/memory phenotype and persistence for effective treatment of ovarian cancer.

Impact

25% of ovarian cancer patients recur within 6 months. Targeting cancer stem cells with a persistent progenitor CAR T cell product offers a potent strategy to address this recurrence.

Major Proposed Activities

• Evaluate tumor associated glycan-specific CAR constructs using in vitro studies by varying extracellular and intracellular signaling domains to optimize for potency and selectivity
• Evaluate multiple antigen-binding domains (i.e., scFv) within optimized CAR construct using in vitro studies.
• Assess anti-tumor efficacy of lead CAR candidates in preclinical human xenograft models of serous ovarian cancer.
• Generate a T cell activation-inducible cytokine production, comparing IL-12 and IL-15, for improved T cell functionality, stem/memory phenotype, and persistence using in vitro studies.
• Optimize CAR T cells with ‘built-in’ inducible cytokine production and identify lead CAR stem/memory T cell therapeutic product using in vitro studies.
• Assess therapeutic efficacy of optimized CAR T cells with ‘built-in’ inducible cytokine production in preclinical human xenograft models of serous ovarian cancer.