Tumor‐reactive CD8+ T‐cell responses after vaccination with NY‐ESO‐1 peptide, CpG 7909 and Montanide® ISA‐51: association with survival

• Published in: International journal of cancer Vol. 126; no. 4; pp. 909 - 918
• Main Authors: Karbach, Julia, Gnjatic, Sacha, Bender, Armin, Neumann, Antje, Weidmann, Eckhart, Yuan, Jianda, Ferrara, Cathy A., Hoffmann, Eric, Old, Lloyd J., Altorki, Nasser K., Jäger, Elke
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.02.2010; Wiley-Blackwell
• Subjects: adjuvants; Antigens, Neoplasm - therapeutic use; Biological and medical sciences; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Cancer Vaccines - therapeutic use; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; clinical outcome; Female; Flow Cytometry; Humans; immune response; Immunotherapy - methods; Mannitol - analogs & derivatives; Mannitol - therapeutic use; Medical sciences; Melanoma - immunology; Membrane Proteins - therapeutic use; Neoplasm Staging; Neoplasms - immunology; Oleic Acids - therapeutic use; Oligodeoxyribonucleotides - therapeutic use; Ovarian Neoplasms - immunology; Ovarian Neoplasms - pathology; peptide‐based vaccination; Sarcoma - immunology; Sarcoma - pathology; Tumors; Vaccination - methods; Prognosis; Immune response; Tumor associated antigen; Peptides; Nucleotide sequence; Vaccination; peptide-based vaccination; Survival; Prevention; Cancerology; GC rich sequence; clinical outcome; Tumor cell; CD8 T lymphocyte; NYESO1 antigen; adjuvants
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.24850

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‐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.