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Approaches to immunology and immunotherapy built on tools and techniques from engineering and the physical sciencesprovide a promising path to the discovery and development of novel treatments for cancer, infectious disease, and autoimmunity. In this talk, 2 example strategies for engineering the immune response will be described, based on a common theme we term “hitchhiking therapeutics”. First, an approach to enhance cellular therapy for cancer will be described:  Adoptive cell therapy (ACT) using patient-derived tumor-specific T-cells is a promising approach for cancer treatment, but strategies to enhance the persistence of ACT T-cell functionality in vivo are still sought. 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, enabled by minimal doses of cytokines that by comparison have no therapeutic effect when given in a soluble form systemically.In a second example, we describe a novel strategy for targeting antigens and immunostimulatory agents to lymph nodes, the anatomical site where immune responses are initiated. A procedure where lymph node targeting is already 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, and provide concepts that may be of utility in regenerative medicine and other related biomedical applications.