Vaccines Combined with Immune Checkpoint Antibodies Promote Cytotoxic T-cell Activity and Tumor Eradication

Cancer Immunol Res. 2016 Feb;4(2):95-100. doi: 10.1158/2326-6066.CIR-14-0126. Epub 2015 Dec 15.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • CTLA-4 Antigen / antagonists & inhibitors
  • Cancer Vaccines / immunology*
  • Disease Models, Animal
  • Female
  • Immunologic Factors / pharmacology*
  • Immunomodulation / drug effects
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Melanoma, Experimental
  • Mice
  • Neoplasms / immunology*
  • Neoplasms / mortality
  • Neoplasms / pathology*
  • Neoplasms / therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • T-Lymphocytes, Cytotoxic / drug effects*
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism

Substances

  • Antibodies, Monoclonal
  • CTLA-4 Antigen
  • Cancer Vaccines
  • Immunologic Factors
  • Programmed Cell Death 1 Receptor