Abstract CT223: Dendritic cells pulsed with Wilms′ tumor gene 1 (WT1)-specific and MHC class I and II-restricted epitopes with gemcitabine induce antitumor immune responses in patients with advanced pancreatic cancer

Abstract

Abstract Wilms' tumor gene 1 (WT1) protein is an attractive target for cancer immunotherapy. To evaluate whether dendritic cells (DCs) pulsed with WT1-specific and MHC class I and II-restricted epitopes in combination with gemcitabine induce antitumor immune responses and improve clinical outcome in patients with advanced pancreatic cancer, we investigated the clinical and immunologic responses to the chemoimmunotherapy. Ten pancreatic cancer patients with stage IV and HLA positive for HLA-A*02:01, A*02:06, A*24:02, DRB1*04:05, DRB1*08:03, DRB1*15:02, DRB1*15:01, DPB1*09:01, or DPB1*05:01 were enrolled in this study. Patients first received gemcitabine on days 1, 8, and 15, followed by intradermal vaccinations with DCs pulsed with MHC class I or II alone (n=3), or MHC-I/II-restricted WT1 peptides (n=7) depending on their HLA biweekly and gemcitabine on days 1, 8, and 15 of a 28-day cycle. In 4 of 7 patients vaccinated with MHC-I/II pulsed DCs and none of 3 patients vaccinated with MHC-I or -II pulsed DCs, we detected WT1 peptide-specific delayed-type hypersensitivity (DTH). Among ten enrolled patients, DTH-positive patients showed significantly improved clinical outcome, compared with negative patients. Moreover, longer survivors featured a higher frequency of memory-phenotype in WT1-specific cytotoxic T-lymphocytes after vaccination with MHC-I/II pulsed DCs. In conclusion, the combination therapy was well-tolerated and activation of WT1-specific immune responses may be associated with improved clinical responses for patients with advanced pancreatic cancer. Citation Format: Shigeo Koido, Sadamu Homma, Masato Okamoto, Masako Mori, Shinji Yoshizaki, Kazuki Takakura, Kazumi Hayashi, Shin Kan, Takafumi Ishidao, Sei-ichi Yusa, Shigetaka Shimodaira, Kan Uchiyama, Mikio Kajihara, Hiroo Imazu, Hiroshi Arakawa, Toshifumi Ohkusa, Hisao Tajiri. Dendritic cells pulsed with Wilms′ tumor gene 1 (WT1)-specific and MHC class I and II-restricted epitopes with gemcitabine induce antitumor immune responses in patients with advanced pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT223. doi:10.1158/1538-7445.AM2014-CT223