Immunization with a peptide containing MHC class I and II epitopes derived from the tumor antigen SIM2 induces an effective CD4 and CD8 T-cell response

PLoS One. 2014 Apr 1;9(4):e93231. doi: 10.1371/journal.pone.0093231. eCollection 2014.

Abstract

Here, we sought to determine whether peptide vaccines designed harbor both class I as well as class II restricted antigenic motifs could concurrently induce CD4 and CD8 T cell activation against autologous tumor antigens. Based on our prior genome-wide interrogation of human prostate cancer tissues to identify genes over-expressed in cancer and absent in the periphery, we targeted SIM2 as a prototype autologous tumor antigen for these studies. Using humanized transgenic mice we found that the 9aa HLA-A*0201 epitope, SIM2(237-245), was effective at inducing an antigen specific response against SIM2-expressing prostate cancer cell line, PC3. Immunization with a multi-epitope peptide harboring both MHC-I and MHC-II restricted epitopes induced an IFN-γ response in CD8 T cells to the HLA-A*0201-restricted SIM2(237-245) epitope, and an IL-2 response by CD4 T cells to the SIM2(240-254) epitope. This peptide was also effective at inducing CD8+ T-cells that responded specifically to SIM2-expressing tumor cells. Collectively, the data presented in this study suggest that a single peptide containing multiple SIM2 epitopes can be used to induce both a CD4 and CD8 T cell response, providing a peptide-based vaccine formulation for potential use in immunotherapy of various cancers.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation / immunology
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / immunology
  • Basic Helix-Loop-Helix Transcription Factors / chemistry
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cancer Vaccines / immunology
  • Cell Line
  • Cytokines / biosynthesis
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / immunology*
  • Gene Expression
  • Gene Expression Profiling
  • HLA-A2 Antigen / immunology
  • Histocompatibility Antigens Class I / immunology*
  • Histocompatibility Antigens Class II / immunology*
  • Humans
  • Immunization
  • Immunotherapy
  • Male
  • Mice
  • Mice, Transgenic
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • Peptides / chemistry
  • Peptides / immunology*
  • Spleen / cytology
  • Spleen / immunology

Substances

  • Antigens, Neoplasm
  • Basic Helix-Loop-Helix Transcription Factors
  • Cancer Vaccines
  • Cytokines
  • Epitopes, T-Lymphocyte
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Peptides
  • SIM2 protein, human