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

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).

Present status and future perspective of peptide‐based vaccine therapy for urological cancer

“…We screened and identified an HLA‐A*2402‐restricted epitope peptide, CDCA1‐A24‐56‐64, that has a high antigenic activity to induce CTL . Recently, we reported a phase I clinical trial for patients with CRPC using a CDCA1 peptide vaccination . Twelve patients having HLA‐A*2402 with CRPC after failure of docetaxel chemotherapy were enrolled.…”

“…29 Recently, we reported a phase I clinical trial for patients with CRPC using a CDCA1 peptide vaccination. 4 RCC until approval of molecular-targeted medicines. Recently, nivolumab (anti-PD-1) showed an OS benefit in patients previously treated with TKI for metastatic RCC, which led to approval.…”

NUF2 Correlates with Poor Prognosis in Non-Small Cell Lung Cancer: A Systematic Multi-Omics Analysis

“…NUF2 is a composition of a molecular linker between the kinetochore attachment site and the tubulin subunits within the lattice of the attached plus ends [19]. NUF2 is also an oncogene that is over-expressed on several cancers [5,20], including lung adenocarcinoma. Comparing with previous study, the NUF2 expression in multiple databases was signi cantly higher than in normal tissues, and also signi cantly higher in LUAD and LUSC [7].…”

A modified HLA-A*0201-restricted CTL epitope from human oncoprotein (hPEBP4) induces more efficient antitumor responses

“…42,43 To evaluate the risk of autoimmunity induction by overexpressed self-antigen-derived peptide vaccinations, several preclinical and clinical trials have demonstrated that peptides derived from overexpressed self-antigens were able to induce effective and specific CTL responses without any serious systemic adverse events. [44][45][46][47] However, studies by Overwijk and Restifo 48 and Overwijk et al 49 revealed that potent CD8 + T-cell responses induced with MDA in melanoma patients could interact with melanocytes in the skin, resulting in autoimmune depigmentation. Therefore, if hPEBP4-derived peptides are to serve as candidates for CTL-based immunotherapy against breast cancer or other hPEBP4-expressing carcinomas, their safety and tolerability need to be further assessed in basic and clinical studies.…”