Events & Seminars > Event Details

Where:

4:00 pm
Room 304, Chemistry Building

Engineering immunity with hitchhiking therapeutics

Speaker:

Professor Darrell Irvine
Massachusetts Institute of Technology

Hosted by: Professor Rebecca Pompano

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) to the surfaces of live lymphocytes for ACT. ACT T-cells carrying cytokine-loaded NPs (to permit pseudo-autocrine self-stimulation following transfer into tumor-bearing hosts) 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 that enable T-cells to be loaded with very high doses of supporting drug will be described, which support their continued expansion/function for up to two weeks in vivo.

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. These examples illustrate the power of bioengineering approaches in shaping the immune response and studying immune cell biology.