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

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.

journal_name

Int J Cancer

authors

Karbach J,Gnjatic S,Pauligk C,Bender A,Maeurer M,Schultze JL,Nadler K,Wahle C,Knuth A,Old LJ,Jäger E

doi

10.1002/ijc.22957

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

2042-8

issue

9

eissn

0020-7136

issn

1097-0215

journal_volume

121

pub_type

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