Tumor-reactive CD8+ T-cell clones in patients after NY-ESO-1 peptide vaccination.
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.
Karbach
Julia
J
II. Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, Frankfurt, Germany.
Gnjatic
Sacha
S
Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, NY.
Pauligk
Claudia
C
II. Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, Frankfurt, Germany.
Bender
Armin
A
II. Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, Frankfurt, Germany.
Maeurer
Markus
M
Microbiology and Tumor Biology Center (MTC), Karolinska Institute, Solna, Sweden.
Schultze
Joachim L
JL
Molekulare Tumorbiologie und Tumorimmunologie, Klinik I für Innere Medizin, Klinikum der Universität zu Köln, Germany.
Nadler
Kerstin
K
II. Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, Frankfurt, Germany.
Wahle
Claudia
C
II. Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, Frankfurt, Germany.
Knuth
Alexander
A
Klinik und Poliklinik für Onkologie, UniversitätsSpital Zürich, Switzerland.
Old
Lloyd J
LJ
Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, NY.
Jäger
Elke
E
II. Medizinische Klinik, Hämatologie-Onkologie, Krankenhaus Nordwest, Frankfurt, Germany.
D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000379:methods*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D012680:Sensitivity and Specificity
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D008565:Membrane Proteins; D010446:Peptide Fragments