Duke Seminar Series: “Engineering Immunity Via Chemistry and Materials Design: Toward an HIV Vaccine and Enhanced Therapies for Cancer”

Darrell J. Irvine, Ph.D., Professor, Depts. of Biological Engineering and Materials Science & Engineering, MIT

Lunch will be served beginning at 11:45 am.

Bio: Darrell Irvine, Ph.D., is a Professor at the Massachusetts Institute of Technology and an Investigator of the Howard Hughes Medical Institute. He also serves on the steering committee of the Ragon Institute of MGH, MIT, and Harvard.  His research is focused on the application of engineering tools to problems in cellular immunology and the development of new materials for vaccine and drug delivery.  Major efforts of the laboratory are directed toward vaccine development for HIV and cancer immunotherapy.  Dr. Irvine’s work has been recognized by numerous awards, including election as a Fellow of the Biomedical Engineering Society, election as a fellow of the American Institute for Medical and Biological Engineering, and appointment as an investigator of the Howard Hughes Medical Institute.  He is the author of over 100 publications, reviews, and book chapters and an inventor on numerous patents.

Abstract: Our laboratory focuses on applying principles from engineering and technologies from materials science, chemistry, and bioengineering to develop new approaches to study the immune system, create new diagnostics, and create next generation vaccines and cancer immunotherapies.  Two examples drawn from our work on HIV vaccines and cancer immunotherapy will be described:  A major goal of HIV vaccine development is the design of vaccines that can elicit broadly neutralizing antibodies (BNAbs), but it remains an unsolved challenge to elicit such antibodies by vaccination.  Working collaboratively with colleagues at the Scripps Research Institute, we have explored strategies to simultaneously enhance the humoral response to engineered HIV env immunogens and direct the specificity of that response.  Using nanoparticles with intrinsic adjuvant activity that bind to the base of stabilized SOSIP trimers, we found that the antibody response to these HIV antigens can be greatly augmented.  In addition, oriented binding of trimers to these particulate adjuvants obscures the base of the trimer, which normally becomes an immunodominant target of the antibody response- thus, these engineered vaccines eliminate a strong non-functional antibody response and redirect B cells to target functional regions of the trimer.    In a second example, a novel strategy for targeting antigens and immunostimulatory agents to lymph nodes for therapeutic cancer vaccines 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.  When combined with complementary immunotherapy agents, these lymph node-targeted vaccines are capable of eradicating large established tumors in several mouse models, providing a blueprint for curative immunotherapies. These examples illustrate the power of bioengineering approaches in shaping the immune response in vivo.