期刊
CLINICAL CANCER RESEARCH
卷 20, 期 16, 页码 4228-4239出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-14-0314
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资金
- Ministry of Education, Cultures, Sports, Science and Technology of Japan
- Foundation for Promotion of Cancer Research
- Mitsui Life Social Welfare Foundation
- Grants-in-Aid for Scientific Research [23501289] Funding Source: KAKEN
Purpose: We performed a phase I trial to investigate the safety, clinical responses, and Wilms' tumor 1 (WT1)-specific immune responses following treatment with dendritic cells (DC) pulsed with a mixture of three types of WT1 peptides, including both MHC class I and II-restricted epitopes, in combination with chemotherapy. Experimental Design: Ten stage IV patients with pancreatic ductal adenocarcinoma (PDA) and 1 patient with intrahepatic cholangiocarcinoma (ICC) who were HLA-positive for A*02:01, A*02:06, A*24:02, DRB1*04:05, DRB1*08:03, DRB1*15:01, DRB1*15:02, DPB1*05:01, or DPB1*09:01 were enrolled. The patients received one course of gemcitabine followed by biweekly intradermal vaccinations with mature DCs pulsed with MHC class I (DC/WT1-I; 2 PDA and 1 ICC), II (DC/WT1-II; 1 PDA), or I/II-restricted WT1 peptides (DC/WT1-I/ II; 7 PDA), and gemcitabine. Results: The combination therapy was well tolerated. WT1-specific IFN gamma-producing CD4(+) T cells were significantly increased following treatment with DC/WT1-I/ II. WT1 peptide-specific delayed-type hypersensitivity (DTH) was detected in 4 of the 7 patients with PDA vaccinated with DC/WT1-I/ II and in 0 of the 3 patients with PDA vaccinated with DC/WT1-I or DC/WT1-II. The WT1-specific DTH-positive patients showed significantly improved overall survival (OS) and progression-free survival (PFS) compared with the negative control patients. In particular, all 3 patients with PDA with strong DTH reactions had a median OS of 717 days. Conclusions: The activation of WT1-specific immune responses by DC/WT1-I/ II combined with chemotherapy may be associated with disease stability in advanced pancreatic cancer. (C) 2014 AACR.
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