Prof. Darrell Irvine, MIT Our laboratory develops synthetic materials as tools to dissect cellular immunology and as delivery agents for new immunotherapies and vaccines. In this talk, 2 examples illustrating work from our laboratory will be described. In the first segment, a new strategy for transcutaneous drug delivery we have termed “microneedle tattooing” will be described. In this approach, we construct multi-layered polymer thin film coatings on skin patch microneedle arrays. The polymer film heterostructure is comprised of a biodegradable polyelectrolyte multilayer carrying proteins, DNA, or RNA, assembled via a layer-by-layer self-assembly process onto an underlying pH-responsive release layer. Application of microneedles to skin leads to rapid dissolution of the release layer and implantation of intact multilayer films into the epidermis, where the film structure allows control over subsequent release of therapeutic cargos over days to weeks. When applied to the delivery of DNA vaccines, we show that this approach achieves efficient transfection in both mouse and non-human primate skin, leading to immune responses comparable to the current gold standard for DNA vaccines, in vivo electroporation. Thus, this technology may provide a route to dry skin patch vaccines that do not require refrigeration, can be self-applied, and achieve efficient transfection in humans. In a second example, we turn to the problem of targeting antigens and immunostimulatory agents to lymph nodes, the anatomical site where immune responses are initiated. A clinical procedure where efficient lymph node targeting is achieved 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 for 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 impressively amplified cellular immune responses and anti-tumor immunity. Together, these examples illustrate powerful new ideas formed at the interface of immunology and engineering.
Biomedical Engineering Seminar: Designing materials for next-generation vaccines and cancer immunotherapies
Thursday, October 24, 2013 2:00pm - 3:00pm