4.7 Article

Immunological evaluation of personalized peptide vaccination for patients with histologically unfavorable carcinoma of unknown primary site

Journal

CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 65, Issue 10, Pages 1223-1231

Publisher

SPRINGER
DOI: 10.1007/s00262-016-1887-5

Keywords

Cancer immunotherapy; Carcinoma of unknown primary site; Metastasis; Personalized peptide vaccine; Unfavorable subsets

Funding

  1. Japan Agency for Medical Research and Development, AMED
  2. Regional Innovation Cluster Program of the Ministry of Education, Culture, Sports, Science and Technology of Japan
  3. Sendai Kousei Hospital

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The immunological characteristics of carcinoma of unknown primary site (CUP) are not well established due to inclusion of heterogeneous types of metastatic tumors with the absence of any detectable primary site. We evaluated the immune responses in patients with histologically unfavorable CUP during personalized peptide vaccination (PPV). Ten patients with histologically unfavorable CUP who had been treated by PPV after chemotherapy failure were analyzed. In PPV treatment, up to four human leukocyte antigen-matched peptides of a total 31 peptides were selected according to preexisting host immunity before vaccination and administered subcutaneously. Peptides derived from the Lck antigen were most often chosen for use among all patients. CTL responses were increased in 8 of the 10 and 5 of the five patients tested at the end of the first and second PPV cycles, respectively. Increases in humoral responses after vaccination, including IgG, IgG1, IgG3, IgA, and IgM, were observed against not only the vaccinated peptides but also the non-vaccinated peptides. Severe adverse events due to PPV were not observed. Median overall survival was 13.9 months (95 % CI 4.0-22.5 months). PPV activated both cellular and humoral immune responses to short peptides derived from CTL epitopes in the majority of CUP patients. PPV with Lck-derived peptides may be a feasible, new treatment modality for histologically unfavorable CUP patients due to its safety and strong ability to boost immune responses, although its clinical efficacy remains to be investigated in larger-scale trials.

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