Tumor-reactive CD8+ T-cell clones in patients after NY-ESO-1 peptide vaccination |
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Authors: | Karbach Julia Gnjatic Sacha Pauligk Claudia Bender Armin Maeurer Markus Schultze Joachim L Nadler Kerstin Wahle Claudia Knuth Alexander Old Lloyd J Jäger Elke |
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Institution: | 1. II. Medizinische Klinik, H?matologie–Onkologie, Krankenhaus Nordwest, Frankfurt, Germany;2. Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan‐Kettering Cancer Center, NY;3. Microbiology and Tumor Biology Center (MTC), Karolinska Institute, Solna, Sweden;4. Molekulare Tumorbiologie und Tumorimmunologie, Klinik I für Innere Medizin, Klinikum der Universit?t zu K?ln, Germany;5. Klinik und Poliklinik für Onkologie, Universit?tsSpital Zürich, Switzerland;6. Fax: +49‐69‐769932. |
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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. |
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Keywords: | tumor immunity peptide vaccination cytotoxic T‐cells tumor cell recognition |
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