Open AccessPhase I clinical trial of cell division associated 1 ( CDCA 1) peptide vaccination for castration resistant prostate cancer
Author(s) -
Obara Wataru,
Sato Fuminori,
Takeda Kazuyoshi,
Kato Renpei,
Kato Yoichiro,
Kanehira Mitsugu,
Takata Ryo,
Mimata Hiromitsu,
Sugai Tamotsu,
Nakamura Yusuke,
Fujioka Tomoaki
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13278
Subject(s) - peptide vaccine , medicine , elispot , prostate cancer , clinical endpoint , ctl* , vaccination , immunology , oncology , cancer , docetaxel , clinical trial , immune system , epitope , t cell , antigen , cd8
Cell division associated 1 ( CDCA 1) 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 CDCA 1 protein was also identified. A phase I clinical trial was conducted for patients with castration resistant prostate cancer ( CRPC ) using a CDCA 1 peptide vaccination. Twelve patients having HLA ‐A*2402 with CRPC after failure of docetaxel chemotherapy were enrolled. They received subcutaneous administration of the CDCA 1 peptide as an emulsion with Montanide ISA 51 VG 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 CDCA 1 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 CDCA 1 peptide were recognized in long‐surviving patients. CDCA 1‐derived peptide vaccine treatment was tolerable and might effectively induce peptide‐specific CTL s for CRPC patients. This novel peptide vaccine therapy for CRPC appears promising. (ClinicalTrials.gov number, NCT 01225471).