Efficient transfer of PSA and PSMA cDNAs into DCs generates antibody and T cell antitumor responses in vivo. Cancer Gene Ther 2005 Jun;12(6):540-51
Date
01/29/2005Pubmed ID
15678150DOI
10.1038/sj.cgt.7700810Scopus ID
2-s2.0-18844416079 (requires institutional sign-in at Scopus site) 24 CitationsAbstract
Gene therapy for prostate cancer may be realized through transduction of whole genes, such as PSA or PSMA, into immunotherapeutic dendritic cells (DCs). An oncoretroviral vector encoding human PSMA and a bicistronic oncoretroviral vector encoding human PSA and cell surface CD25 cDNAs were constructed. Remarkably, transfer of PSA/CD25 or PSMA cDNA during murine hematopoietic cell differentiation into DCs occurred with approximately 80% efficiency. In vitro, transduced DCs retained allostimulatory function and primed syngeneic T cells for tumor antigen-specific IFN-gamma secretion. In test experiments designed to elucidate mechanisms in vivo, syngeneic recipients of transduced DCs had increased anti-human PSA antibody titers and tumor-specific CD8(+) T cell IFN-gamma secretion with no detectable immune response to CD25. Gene-modified DC recipients had increased protection from specific tumor challenge for at least 18 weeks post-vaccination. DC vaccination also protected both male and female recipients. Gene-modified DC vaccination mediated regression of established, specific gene-expressing, TRAMP-C1 prostate cancer cell tumors. These findings indicate that antibody and cellular responses generated through PSA and PSMA gene transfer into DC yielded protective immunity, thereby providing further preclinical support for the implementation of immuno-gene therapy approaches for prostate cancer.
Author List
Medin JA, Liang SB, Hou JW, Kelley LS, Peace DJ, Fowler DHAuthor
Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntibodies, Neoplasm
Antigens, Surface
CD8-Positive T-Lymphocytes
Cancer Vaccines
DNA, Complementary
Dendritic Cells
Female
Genetic Therapy
Genetic Vectors
Glutamate Carboxypeptidase II
Humans
Male
Mice
Prostate-Specific Antigen
Prostatic Neoplasms
Receptors, Interleukin-2
