Tumor-reactive CD8+ T-cell clones in patients after NY-ESO-1 peptide vaccination Journal Article
| Authors: | Karbach, J.; Gnjatic, S.; Pauligk, C.; Bender, A.; Maeurer, M.; Schultze, J. L.; Nadler, K.; Wahle, C.; Knuth, A.; Old, L. J.; Jager, E. |
| Article Title: | 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 post-vaccine 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. |
| Keywords: | human cell; case report; sensitivity and specificity; neoplasms; cd8+ t lymphocyte; cd8-positive t-lymphocytes; cells, cultured; membrane proteins; patient monitoring; cell line, tumor; mixed lymphocyte culture; dendritic cells; cellular immunity; antigens, neoplasm; cancer vaccines; ny eso 1 antigen; antigen recognition; peptide fragments; vaccination; cytotoxic t lymphocyte; tumor immunity; cell separation; antigen presenting cell; hla a2 antigen; cpg 7909; cytotoxic t-cells; peptide vaccination; tumor cell recognition |
| Journal Title: | International Journal of Cancer |
| Volume: | 121 |
| Issue: | 9 |
| ISSN: | 0020-7136 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2007-11-01 |
| Start Page: | 2042 |
| End Page: | 2048 |
| Language: | English |
| DOI: | 10.1002/ijc.22957 |
| PUBMED: | 17640060 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 15" - "Export Date: 17 November 2011" - "CODEN: IJCNA" - "Source: Scopus" |
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