Combination of p53-DC vaccine and rAd-p53 gene therapy induced CTLs cytotoxic against p53-deleted human prostate cancer cells in vitro

• DOI: 10.1038/cgt.2017.21
• Publication Date: 2017-06-16T10:20:37Z
• Authors: H Saito; K Kitagawa; T Yoneda; Y Fukui; M Fujsawa; D Bautista; T Shirakawa
• Keywords: Cytotoxicity, Immunologic; Male; Perforin; Genetic Vectors; Gene Expression; Prostatic Neoplasms; Dendritic Cells; Genetic Therapy; Cancer Vaccines; Immunohistochemistry; Adenoviridae; 3. Good health; 03 medical and health sciences; Phenotype; 0302 clinical medicine; Cell Line, Tumor; Humans; Tumor Suppressor Protein p53; Biomarkers; T-Lymphocytes, Cytotoxic

Recently, the US FDA approved sipuleucel-T, which is composed of autologous DCs stimulated with a recombinant fusion protein of prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GM-CSF), as the first immunotherapeutic agent for metastatic castration resistant prostate cancer (mCRPC). However, sipuleucel-T demonstrated only modest efficacy in mCPRC patients. Researchers are now investigating the potential of p53 protein as a tumor-associated antigen (TAA) loaded in DC-based cancer vaccine. Approximately half of all tumors overexpress p53, and up to 20% of prostate cancer cells overexpresses p53. In this study, we evaluated the feasibility of combining p53-DC vaccine and rAd-p53 gene therapy, using the p53-overexpressing and non-expressing prostate cancer cells in vitro. We successfully generated the p53-DC vaccine by culturing autologous DCs infected with rAd-p53. This p53-DC vaccine can differentiate CTLs specifically cytotoxic to p53-overexpressing prostate cancer cells. In addition, rAd-p53 infection can induce overexpression of p53 and thus the cytotoxicity of CTLs differentiated by the p53-DC vaccine in p53 non-expressing prostate cancer cells. These findings suggest that this combination therapy using p53-DC vaccine and rAd-p53 gene therapy together may represent a new paradigm for the treatment of mCRPC.