The Department of Chemistry invites you to its departmental seminar Monday, Sept. 12, at 4:10 p.m. in Fulmer Hall, room 201.
Dr. Darrell Irvine from Massachusetts Institute of Technology will present, Engineering immunity against cancer
Abstract: We have recently focused on engineering strategies to enhanced vaccines and immunotherapy based on two different approaches to the design of “hitchhiking” therapeutics: First, an approach to enhance adoptive cell therapy (ACT) for cancer will be described. ACT using patient-derived tumor-specific T-cells is a promising approach for cancer treatment, but strategies to enhance ACT T-cell functionality in vivo are needed. We developed a strategy combining nanomedicine with ACT, based on the chemical conjugation of drug-loaded nanoparticles (NPs) as synthetic “backpacks” to the surfaces of live lymphocytes for ACT. ACT T-cells backpacked with cytokine-loaded NPs are capable of massive in vivo expansion and robust anti-tumor responses, while avoiding side effects commonly observed with systemically-administered immunomodulatory drugs. Novel protein nanogels backpacks will be described that release supporting drugs to T cells in response to signaling through the cells’ antigen receptors, further enabling tissue- and target-specific drug delivery.
Second, a novel strategy for targeting antigens and immunostimulatory agents to lymph nodes will be described. Lymph node targeting is achieved clinically is sentinel lymph node mapping in cancer patients, where small-molecule dyes are efficiently delivered to lymph nodes by binding to serum albumin. To mimic this process in vaccine delivery, we synthesized amphiphiles designed to non-covalently bind vaccine antigens and adjuvants to endogenous albumin. These “albumin-hitchhiking” amphiphiles were efficiently delivered to lymph nodes following injection, leading to as much as 30-fold amplified cellular immune responses and anti-tumor immunity. In ongoing preclinical studies, we have discovered combination immunotherapies that leverage these very potent engineered peptide vaccines to eradicate established immunosuppressive tumors in a majority of treated animals, providing proof of concept that the endogenous immune system is capable of eliminating large established tumors. These examples illustrate the power of bioengineering approaches in shaping the immune response and studying immune cell biology.
