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(R) 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-A2+ 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 NY-ESO-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.

• Authors: Julia Karbach, Sacha Gnjatic, Armin Bender, Antje Neumann, Eckhart Weidmann, Jianda Yuan, Cathy A Ferrara, Eric Hoffmann, Lloyd J Old, Nasser K Altorki, Elke Jäger
• Journal: International journal of cancer (Int J Cancer) Vol. 126 Issue 4 Pg. 909-18 (Feb 15 2010) ISSN: 1097-0215 [Electronic] United States
• PMID: 19728336 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• CTAG1B protein, human
• Cancer Vaccines
• Membrane Proteins
• Oleic Acids
• Oligodeoxyribonucleotides
• ProMune
• montanide ISA 51
• Mannitol

Topics

• Antigens, Neoplasm (therapeutic use)
• Breast Neoplasms (immunology, pathology)
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (therapeutic use)
• Cell Line, Tumor
• Female
• Flow Cytometry
• Humans
• Immunotherapy (methods)
• Mannitol (analogs & derivatives, therapeutic use)
• Melanoma (immunology)
• Membrane Proteins (therapeutic use)
• Neoplasm Staging
• Neoplasms (immunology)
• Oleic Acids (therapeutic use)
• Oligodeoxyribonucleotides (therapeutic use)
• Ovarian Neoplasms (immunology, pathology)
• Sarcoma (immunology, pathology)
• Vaccination (methods)