期刊
ONCOIMMUNOLOGY
卷 5, 期 10, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2016.1216290
关键词
CpG-B; HLA-DR7; long synthetic peptide; malignant melanoma; NY-ESO-1
资金
- Cancer Research Institute (USA)
- Ludwig Cancer Research (USA)
- Cancer Vaccine Collaborative (USA)
- Atlantic Philanthropies (USA)
- Wilhelm Sander-Foundation (Germany)
- Swiss Cancer Research [3507-08-2014]
- Swiss National Science Foundation [CRSII3_160708, 320030_152856, 31003A_163204, 310030-130812]
- SwissTransMed [KIP 18]
Long synthetic peptides and CpG-containing oligodeoxynucleotides are promising components for cancer vaccines. In this phase I trial, 19 patients received a mean of 8 (range 1-12) monthly vaccines s.c. composed of the long synthetic NY-ESO-1(79-108) peptide and CpG-B (PF-3512676), emulsified in Montanide ISA-51. In 18/18 evaluable patients, vaccination induced antigen-specific CD8(+) and CD4(+) T-cell and antibody responses, starting early after initiation of immunotherapy and lasting at least one year. The T-cells responded antigen-specifically, with strong secretion of IFN and TNF, irrespective of patients' HLAs. The most immunogenic regions of the vaccine peptide were NY-ESO-1(89-102) for CD8(+) and NY-ESO-1(83-99) for CD4(+) T-cells. We discovered a novel and highly immunogenic epitope (HLA-DR7/NY-ESO-1(87-99)); 7/7 HLA-DR7(+) patients generated strong CD4(+) T-cell responses, as detected directly ex vivo with fluorescent multimers. Thus, vaccination with the long synthetic NY-ESO-1(79-108) peptide combined with the strong immune adjuvant CpG-B induced integrated, robust and functional CD8(+) and CD4(+) T-cell responses in melanoma patients, supporting the further development of this immunotherapeutic approach.
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