Tumor-reactive CD8+ T-cell responses after vaccination with NY-ESO-1 peptide, CpG 7909 and Montanide® ISA-51: Association with survival Journal Article
| Authors: | Karbach, J.; Gnjatic, S.; Bender, A.; Neumann, A.; Weidmann, E.; Yuan, J.; Ferrara, C. A.; Hoffmann, E.; Old, L. J.; Altorki, N. K.; Jager, E. |
| Article Title: | Tumor-reactive CD8+ T-cell responses after vaccination with NY-ESO-1 peptide, CpG 7909 and Montanide® ISA-51: Association with survival |
| Abstract: | Peptide-based vaccines have led to the induction of antigen-specific CD8+ T-cell responses in patients with NY-ESO-1 positive cancers. However, vaccine-induced T-cell responses did not generally correlate with improved survival. Therefore, we tested whether a synthetic CpG 7909 ODN (deoxycytidyl-deoxyguanosin oligodeoxy-nucleotides) mixed with NY-ESO-1 peptide p157-165 and incomplete Freund's adjuvants (Montanide® ISA-51) led to enhanced NY-ESO-1 antigen-specific CD8+ immune responses in patients with NY-ESO-1 or LAGE-1 expressing tumors. Of 14 HLA-A21 patients enrolled in the study, 5 patients withdrew prematurely because of progressive disease and 9 patients completed 1 cycle of immunization. Nine of 14 patients developed measurable and sustained antigen-specific CD8+ T-cell responses: Four had detectable CD8+ T-cells against NYESO-1 after only 2 vaccinations, whereas 5 patients showed a late-onset but durable induction of NY-ESO-1 p157-165 specific T-cell response during continued vaccination after 4 months. In 6 patients, vaccine-induced antigen-specific T-cells became detectable ex vivo and reached frequencies of up to 0.16 % of all circulating CD8+ T-cells. Postvaccine T-cell clones were shown to recognize and lyse NY-ESO-1 expressing tumor cell lines in vitro. In 6 of 9 patients developing NY-ESO-1-specific immune responses, a favorable clinical outcome with overall survival times of 43+, 42+, 42+, 39+, 36+ and 27+ months, respectively, was observed. © 2009 UICC. |
| Keywords: | clinical trial; flow cytometry; neoplasm staging; neoplasms; cd8+ t lymphocyte; cd8-positive t-lymphocytes; ovarian neoplasms; melanoma; multiple cycle treatment; ovary cancer; breast cancer; lung non small cell cancer; membrane proteins; cell line, tumor; breast neoplasms; sarcoma; immune response; immunotherapy; antigens, neoplasm; cancer vaccines; antigen specificity; ny eso 1 antigen; montanide isa 51; vaccination; agatolimod; phase 1 clinical trial; mannitol; adjuvants; hla a2 antigen; oligodeoxyribonucleotides; clinical outcome; peptide-based vaccination; oleic acids |
| Journal Title: | International Journal of Cancer |
| Volume: | 126 |
| Issue: | 4 |
| ISSN: | 0020-7136 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2010-02-15 |
| Start Page: | 909 |
| End Page: | 918 |
| Language: | English |
| DOI: | 10.1002/ijc.24850 |
| PUBMED: | 19728336 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 9" - "Export Date: 20 April 2011" - "CODEN: IJCNA" - "Source: Scopus" |
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