Tumor-reactive CD8+ T-cell clones in patients after NY-ESO-1 peptide vaccination

Int J Cancer. 2007 Nov 1;121(9):2042-8. doi: 10.1002/ijc.22957.

Abstract

A major objective of peptide vaccination is the induction of tumor-reactive CD8+ T-cells. We have shown that HLA-A2 positive cancer patients frequently develop an antigen-specific CD8+ T-cell response after vaccination with NY-ESO-1 peptides p157-165/p157-167. These T-cells are highly reactive with the peptides used for vaccination, but only rarely recognize HLA-matched, NY-ESO-1 expressing tumor cell lines. To address the apparent lack of tumor recognition of vaccine-induced CD8+ T-cell responses, we used autologous tumor cells for in vitro stimulation and expansion of pre- and postvaccine CD8+ T-cells. In contrast to standard presensitization methods with peptide-pulsed antigen-presenting cells, mixed lymphocyte tumor culture favored the selective expansion of low-frequency tumor-reactive T-cells. In four patients, we were able to demonstrate that antigen-specific and tumor-reactive T-cells are detectable and are indeed elicited as a result of NY-ESO-1 peptide vaccination. Further analyses of postvaccine antigen-specific T-cells at a clonal level show that vaccine-induced antigen-specific T-cells are heterogeneous in functional activity. These results suggest that the methods of immunomonitoring are critical to identify the proportion of tumor-reactive T-cells within the population of vaccine-induced antigen-specific effector cells. Our results show that immunization with NY-ESO-1 peptides leads to strong tumor-reactive CD8+ T-cell responses. Our findings suggest that approaches to peptide vaccination may be improved to induce higher numbers of antigen-specific T-cells and to selectively increase the proportion of CD8+ T-cells that have the capacity to recognize and eliminate tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Cell Separation / methods*
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Humans
  • Membrane Proteins / immunology*
  • Neoplasms / immunology*
  • Peptide Fragments / immunology*
  • Sensitivity and Specificity

Substances

  • Antigens, Neoplasm
  • CTAG1B protein, human
  • Cancer Vaccines
  • Membrane Proteins
  • Peptide Fragments