Tumor-Specific CD8+ T-Cell Responses Induced by DNA Vaccination

Methods Mol Biol. 2021:2197:225-239. doi: 10.1007/978-1-0716-0872-2_12.

Abstract

DNA vaccines assisted by electroporation efficiently trigger antitumor cytotoxic CD8+ T cell responses in preclinical cancer models and hold potential for human use. They can be easily engineered to express either tumor-associated self-antigens, which are broadly expressed among tumor patients but also in healthy tissue, or tumor-specific neoantigens, which are uniquely expressed in tumors and differ among patients. Recently, it has been demonstrated that DNA vaccination generates both circulating and tissue-resident compartments of CD8+ T cells, which act concertedly against tumors. Here we describe the steps to obtain and test DNA vaccines against models of self-antigens and neoantigens in mice. It includes the evaluation of effector and memory CD8+ T cell responses, as well as assessing the antitumor potential in vivo using transplantable syngeneic tumor models.

Keywords: Antitumor immunity; CD8+ T cells; Circulating memory T cells; DNA vaccine; Flow cytometry; Immunization; Resident memory T cells; Tumor model.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, Neoplasm / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Humans
  • Immunization
  • Immunologic Memory
  • Immunophenotyping
  • Mice
  • Neoplasms / immunology
  • Neoplasms / therapy
  • T-Cell Antigen Receptor Specificity / immunology*
  • Treatment Outcome
  • Vaccination
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology*
  • Xenograft Model Antitumor Assays

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Vaccines, DNA