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Cancer Gene Ther ; 24(7): 289-296, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28621316

ABSTRACT

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.


Subject(s)
Cancer Vaccines/immunology , Dendritic Cells/immunology , Dendritic Cells/metabolism , Genetic Therapy , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Cytotoxic/metabolism , Tumor Suppressor Protein p53/genetics , Adenoviridae/genetics , Biomarkers , Cell Line, Tumor , Cytotoxicity, Immunologic , Gene Expression , Genetic Therapy/methods , Genetic Vectors/genetics , Humans , Immunohistochemistry , Male , Perforin , Phenotype , Prostatic Neoplasms/genetics , Prostatic Neoplasms/immunology , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Tumor Suppressor Protein p53/metabolism
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