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

✍ Scribed by Julia Karbach; Sacha Gnjatic; Claudia Pauligk; Armin Bender; Markus Maeurer; Joachim L. Schultze; Kerstin Nadler; Claudia Wahle; Alexander Knuth; Lloyd J. Old; Elke Jäger

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: French
• Weight: 272 KB
• Volume: 121
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.22957

✦ Synopsis

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. © 2007 Wiley‐Liss, Inc.