Phase I clinical trial of cell division associated 1 (CDCA1) peptide vaccination for castration resistant prostate cancer

Wataru Obara, Fuminori Sato, Kazuyoshi Takeda, Renpei Kato, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata, Hiromitsu Mimata, Tamotsu Sugai, Yusuke Nakamura, Tomoaki Fujioka, Wataru Obara, Fuminori Sato, Kazuyoshi Takeda, Renpei Kato, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata, Hiromitsu Mimata, Tamotsu Sugai, Yusuke Nakamura, Tomoaki Fujioka

Abstract

Cell division associated 1 (CDCA1) was screened as an oncogene that is overexpressed on several cancers, including prostate cancer. A highly immunogenic HLA-A*2402-restricted epitope peptide corresponding to part of the CDCA1 protein was also identified. A phase I clinical trial was conducted for patients with castration resistant prostate cancer (CRPC) using a CDCA1 peptide vaccination. Twelve patients having HLA-A*2402 with CRPC after failure of docetaxel chemotherapy were enrolled. They received subcutaneous administration of the CDCA1 peptide as an emulsion with Montanide ISA51VG once a week in a dose-escalation manner (doses of 1.0 or 3.0 mg/body, six patients received each dose). The primary endpoint was safety, and the secondary endpoints were the immunological and clinical responses. Vaccination with CDCA1 peptide was well tolerated without any serious adverse events. Peptide-specific cytotoxic T lymphocyte (CTL) responses using ELISPOT assay and dextramer assay were observed in three patients receiving the 1.0 mg dose and five patients receiving the 3.0 mg dose. The median overall survival time was 11.0 months and specific CTL reacting to CDCA1 peptide were recognized in long-surviving patients. CDCA1-derived peptide vaccine treatment was tolerable and might effectively induce peptide-specific CTLs for CRPC patients. This novel peptide vaccine therapy for CRPC appears promising. (ClinicalTrials.gov number, NCT01225471).

Keywords: Cancer peptide vaccine; castration resistant prostate cancer; cell division associated 1; oncogene; peptide specific CTL.

© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Figures

Figure 1
Figure 1
Representative CDCA1 peptide‐specific CTL responses. peripheral blood lymphocytes obtained from patient case 8 pre‐vaccination and after the 3rd vaccination were cultured in rIL‐2 for 14 days with 2 CDCA1‐peptide stimulations. (a) The cultured lymphocytes were subjected to ELISPOT assay after depletion of CD4‐positive cells by magnetic beads. TISI cells were incubated with responder cells in the presence of CDCA1 peptide or HIV peptide as an irrelevant control, and the spot counts were quantified (b). (c) The cultured lymphocytes were analyzed with HLA‐A2402/HIV‐dextramer pre vaccination (left) or HLA‐A2402/CDCA1‐dextramer (right) combined with anti‐CD8 and ‐CD3 mAbs by flow cytometry. The value of dextramer (+)/CD8(+) cells among CD3(+) cells is shown. R/S, responder/stimulator.
Figure 2
Figure 2
Overall survival of CDCA1 peptide vaccine therapy patients. Total median overall survival (OS) was 25.8 months (a). According to peptide‐specific CTL responses, the CTL strong response group showed a significantly longer OS than the CTL negative/weak response group (OS; not reached versus 4.6 months, P = 0.0040) (b).

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