title: Engineering New Approaches to Cancer Vaccines.
abstract: Recently, a number of promising approaches have been developed using synthetic chemistry, materials science, and bioengineering-based strategies to address challenges in the design of more effective cancer vaccines. At the stage of initial priming, potency can be improved by maximizing vaccine delivery to lymph nodes. Because lymphatic uptake from peripheral tissues is strongly size dependent, antigens and adjuvants packaged into optimally sized nanoparticles access the lymph node with much greater efficiency than unformulated vaccines. Once primed, T cells must home to the tumor site. Because T cells acquire the necessary surface receptors in the local lymph node draining the tissue of interest, vaccines must be engineered that reach organs, such as the lung and gut, which are common sites of tumor lesions but inaccessible by traditional vaccination routes. Particulate vaccine carriers can improve antigen exposure in these organs, resulting in greater lymphocyte priming. Immunomodulatory agents can also be injected directly into the tumor site to stimulate a systemic response capable of clearing even distal lesions; materials have been designed that entrap or slowly release immunomodulators at the tumor site, reducing systemic exposure and improving therapeutic efficacy. Finally, lessons learned from the design of biomaterial-based scaffolds in regenerative medicine have led to the development of implantable vaccines that recruit and activate antigen-presenting cells to drive antitumor immunity. Overall, these engineering strategies represent an expanding toolkit to create safe and effective cancer vaccines.
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts.
authors.forename: Naveen K
authors.initials: NK
authors.lastname: Mehta
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts. Ragon Institute of MGH, MIT and Harvard University, Boston, Massachusetts.
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Moynihan
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts. Ragon Institute of MGH, MIT and Harvard University, Boston, Massachusetts. Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts. Howard Hughes Medical Institute, Chevy Chase, Maryland. djirvine@mit.edu.
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: Irvine
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008198:Lymph Nodes / Q000276:immunology; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines