PhD Proposal Defense: Michael Zhang

B cells are an alternative source of APCs for therapeutic cancer vaccines due to their relative abundance in the peripheral blood and relatively high proliferation potential compared to DCs. The natural biology of B cells enables antigen-specific B-cell uptake and presentation to CD4⁺ T cells, but not efficient non-specific uptake and presentation to naïve CD8⁺ T cells, hindering translation of B-cell carriers for therapeutic cancer vaccines. I propose lipid-conjugation of antigens and adjuvants will provide a modular delivery system that can induce B cells to carry lipid-tailed cargo for enhanced priming of CD4⁺ and CD8⁺ T cells. My proposed aims are 1) to synthesize and deliver lipid-conjugated antigens to B cells for increased presentation, 2) to deliver lipid coupled adjuvants to B cells for enhanced adjuvant efficacy, and 3) to prime CD4⁺ and CD8⁺ T cells with loaded B-cell carriers for enhanced anti-tumor immunity. The use of lipid-conjugation to facilitate delivery to B cells will allow for a modular platform of delivering antigen and adjuvant combinations that are best suited for inducing T-cell immunity and reveal underappreciated B-cell biology that can be exploited for therapeutic B-cell carrying vaccines in cancer and other chronic diseases.