Tumor endothelial marker 1-specific DNA vaccination targets tumor vasculature

J Clin Invest. 2014 Apr;124(4):1497-511. doi: 10.1172/JCI67382. Epub 2014 Mar 18.

Abstract

Tumor endothelial marker 1 (TEM1; also known as endosialin or CD248) is a protein found on tumor vasculature and in tumor stroma. Here, we tested whether TEM1 has potential as a therapeutic target for cancer immunotherapy by immunizing immunocompetent mice with Tem1 cDNA fused to the minimal domain of the C fragment of tetanus toxoid (referred to herein as Tem1-TT vaccine). Tem1-TT vaccination elicited CD8+ and/or CD4+ T cell responses against immunodominant TEM1 protein sequences. Prophylactic immunization of animals with Tem1-TT prevented or delayed tumor formation in several murine tumor models. Therapeutic vaccination of tumor-bearing mice reduced tumor vascularity, increased infiltration of CD3+ T cells into the tumor, and controlled progression of established tumors. Tem1-TT vaccination also elicited CD8+ cytotoxic T cell responses against murine tumor-specific antigens. Effective Tem1-TT vaccination did not affect angiogenesis-dependent physiological processes, including wound healing and reproduction. Based on these data and the widespread expression of TEM1 on the vasculature of different tumor types, we conclude that targeting TEM1 has therapeutic potential in cancer immunotherapy.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cell Line, Tumor
  • Female
  • Humans
  • Immune Tolerance
  • Immunodominant Epitopes
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Microvessels / immunology
  • Microvessels / pathology
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology*
  • Neoplasms, Experimental / blood supply*
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / therapy*
  • Pregnancy
  • Tetanus Toxoid / genetics
  • Tetanus Toxoid / immunology
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology
  • Vaccines, DNA / therapeutic use*

Substances

  • Antigens, CD
  • Cancer Vaccines
  • Immunodominant Epitopes
  • Neoplasm Proteins
  • Tetanus Toxoid
  • Vaccines, DNA
  • tumor endothelial marker 1, mouse