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Tumor‐reactive CD8 + T‐cell responses after vaccination with NY‐ESO‐1 peptide, CpG 7909 and Montanide® ISA‐51: association with survival
Author(s) -
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
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24850
Subject(s) - antigen , cd8 , immunology , immune system , vaccination , medicine , cytotoxic t cell , t cell , biology , in vitro , biochemistry
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.