Abstract 2539: Clinical prospective study of PepTivator® WT1-pulsed DC vaccines with assessment of immunological responses in solid tumors
Authors: Saiwaki Shoko , Goto Shigenori , Takahara Masashi , Matsushita Haruka , Kondo Takashige , Bohnenkamp Hermann , Maekawa Ryuji , Kamigaki Takashi 
Published: May 2015

Abstract
Wilms' tumor gene 1 (WT1) is reported to be expressed in various types of malignancies and be one of promising target antigens for cancer immunotherapy. However, the synthetic short peptide vaccines based on the WT1 sequences limit a candidate patient by its HLA restriction. In this study, we performed the clinical study for dendritic cell (DC) vaccines using peptide pools consisting mainly of 15-mer sequences with 11 amino acids overlaps of full-length WT1 protein (PepTivator® WT1). We previously reported that copulsing tumor antigen-pulsed DC with zoledronate (Zol) could efficiently enhance expansion of tumor antigen specific CD8+ T cells by activation of gamma-delta T cells. In the present study, we studied the immunological response induced by PepTivator® WT1-pulsed Zol-DC vaccines in solid tumors, and also investigated the feasibility and safety of PepTivator® WT1-pulsed Zol-DC vaccines.
Five patients with WT1-positive solid tumor (ovary: 4, lung: 1) were enrolled. PBMCs were collected by leukapheresis from the patients and the adherent cell fraction was differentiated into DCs by conventional method. In this vaccine therapy, PepTivator® WT1-pulsed Zol-DC (more than 5x106 cells per injection) was administered to patients subcutaneously for six times every two weeks. In order to examine the specific immune responses to WT1 antigen, PBMCs before therapy (pre-PBMC) and PBMCs after therapy (post-PBMC) were in vitro restimulated with PepTivator® WT1-pulsed Zol-DCs for 14 days and the expanded cells were separated into CD8+ cells and CD4+ cells by MACS, and the antigen specific IFN-gamma- producing cells were detected by ELISpot assay.
As a result, no serious adverse events were seen in three patients who had completed all DC vaccines (Patient ID: #1, #2 and #5). DTH reaction was observed in all three patients. During in vitro restimulation and expansion, there was more than three-fold higher expansion of T cells responding to PepTivator® WT1-pulsed Zol-DC in post-PBMC compared to pre-PBMC among two of three patients (#1, #2). In these two patients, the antigen specific IFN-gamma-producing cells were detected in CD8+ T cells from post-PBMC, but not from pre-PBMC. As for CD4+ T cells, however, the antigen specific IFN-gamma-producing cells were not detected, neither in pre-PBMC, nor in post-PBMC.
We found that PepTivator® WT1-pulsed Zol-DC vaccines are feasible and safe, and can induce antigen specific CD8+ T cells. We need more extensive investigation for the immunological monitoring and clinical outcome.
Citation Format: Shoko Saiwaki, Shigenori Goto, Masashi Takahara, Haruka Matsushita, Takashige Kondo, Hermann Bohnenkamp, Ryuji Maekawa, Takashi Kamigaki. Clinical prospective study of PepTivator® WT1-pulsed DC vaccines with assessment of immunological responses in solid tumors. [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 2539. doi:10.1158/1538-7445.AM2014-2539