title: Vaccines Combined with Immune Checkpoint Antibodies Promote Cytotoxic T-cell Activity and Tumor Eradication.
abstract: We demonstrate that a poly(lactide-co-glycolide) (PLG) cancer vaccine can be used in combination with immune checkpoint antibodies, anti-CTLA-4 or anti-PD-1, to enhance cytotoxic T-cell (CTL) activity and induce the regression of solid B16 tumors in mice. Combination therapy obviated the need for vaccine boosting and significantly skewed intratumoral reactions toward CTL activity, resulting in the regression of B16 tumors up to 50 mm(2) in size and 75% survival rates. These data suggest that combining material-based cancer vaccines with checkpoint antibodies has the potential to mediate tumor regression in humans.
authors.affiliation: Wyss Institute for Bioinspired Engineering, Harvard University, Boston, Massachusetts. School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts.
authors.forename: Omar A
authors.initials: OA
authors.lastname: Ali
authors.affiliation: Wyss Institute for Bioinspired Engineering, Harvard University, Boston, Massachusetts.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Lewin
authors.affiliation: Novartis Institute for BioMedical Research, Exploratory Immuno-Oncology, Cambridge, Massachusetts.
authors.forename: Glenn
authors.initials: G
authors.lastname: Dranoff
authors.affiliation: Wyss Institute for Bioinspired Engineering, Harvard University, Boston, Massachusetts. School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts. mooneyd@seas.harvard.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D019496:Cancer Vaccines / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology*; D056747:Immunomodulation / Q000187:drug effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008546:Melanoma, Experimental; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; D019496:Cancer Vaccines; D007155:Immunologic Factors; D061026:Programmed Cell Death 1 Receptor