Journal
CLINICAL IMMUNOLOGY
Volume 166, Issue -, Pages 48-58Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2016.03.015
Keywords
Translational research; Five-peptide cancer vaccine; Cyclophosphamide; Regulatory T cells
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Funding
- Japanese Ministry of Education, Culture, Sports, Science, and Technology [20790498]
- Grants-in-Aid for Scientific Research [16K07141, 15K14410, 20790498] Funding Source: KAKEN
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We designed a phase I trial to investigate the safety, immune responses and clinical benefits of a five-peptide cancer vaccine in combination with chemotherapy. Study subjects were patients positive for HLA-A2402 with locally advanced, metastatic, and/or recurrent gastrointestinal, lung or cervical cancer. Eighteen patients including nine cases of colorectal cancer were treated with escalating doses of cyclophosphamide 4 days before vaccination. Five HLA-A2402-restricted, tumor-associated antigen (TAA) epitope peptides from KOC1, TTK, URLC10, DEPDC1 and MPHOSPH1 were injected weekly for 4 weeks. Treatment was well tolerated without any adverse events above grade 3. Analysis of peripheral blood lymphocytes showed that the number of regulatory T cells dropped from baseline after administration of cyclophosphamide and confirmed that TAA-specific T cell responses were associated significantly with longer overall survival. This phase I clinical trial demonstrated safety and promising immune responses that correlated with vaccine-induced T-cell responses. Therefore, this approach warrants further clinical studies. (C) 2016 Elsevier Inc. All rights reserved.
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