Impact of synchronized anti-PD-1 with Ad-CEA vaccination on inhibition of colon cancer growth

Immunotherapy. 2019 Aug;11(11):953-966. doi: 10.2217/imt-2019-0055. Epub 2019 Jun 13.

Abstract

Aim: The purpose of this study was to determine whether addition of anti-PD-1 antibody increased the immunogenicity and anti-tumor activity of Ad-CEA vaccination in a murine model of colon cancer. Methods: Ad-CEA was administered prior to implantation of MC-38-CEA cells followed by administration of anti-PD-1 antibody. CEA-specific T-cell responses were measured by flow cytometry and ELISPOT. Dynamic co-culture of splenocytes with tumor cells was conducted to analyze anti-tumor activities. Tumor infiltration by lymphocytes was measured by IHC. Tumor volume and overall survival were also recorded. Results: Ad-CEA combined with anti-PD-1 antibody showed greater anti-tumor activity compared with either alone. The combination also increased T-cell infiltration but decreased Tregs. Conclusion: Combining Ad-CEA vaccination with anti-PD-1 antibody enhanced anti-tumor activity and immune responses.

Keywords: CEA; PD-1 blockade; colon cancer; immunotherapy; microenvironment; tumor vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae*
  • Animals
  • Antineoplastic Agents, Immunological / pharmacology*
  • Cancer Vaccines* / genetics
  • Cancer Vaccines* / immunology
  • Carcinoembryonic Antigen* / genetics
  • Carcinoembryonic Antigen* / immunology
  • Cell Line, Tumor
  • Colonic Neoplasms* / genetics
  • Colonic Neoplasms* / immunology
  • Colonic Neoplasms* / pathology
  • Colonic Neoplasms* / therapy
  • Female
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Neoplasms, Experimental* / genetics
  • Neoplasms, Experimental* / immunology
  • Neoplasms, Experimental* / pathology
  • Neoplasms, Experimental* / therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / immunology
  • Vaccination*

Substances

  • Antineoplastic Agents, Immunological
  • Cancer Vaccines
  • Carcinoembryonic Antigen
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor