| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Department of Surgery, Division of Urology, Departments of
Surgery and
Pathology, and
Center for Genetic and Cellular Therapies, Duke University Medical Center, Durham, NC 27710
Polyvalent cancer vaccines targeting the entire antigenic spectrum on tumor cells may represent a superior therapeutic strategy for cancer patients than vaccines solely directed against single Ags. In this study, we show that autologous dendritic cells (DC) transfected with RNA amplified from microdissected tumor cells are capable of stimulating CTL against a broad set of unidentified and critical prostate-specific Ags. Although the polyclonal CTL responses generated with amplified tumor RNA-transfected DC encompassed as a subcomponent a response against prostate-specific Ag (PSA) as well as against telomerase reverse transcriptase, the tumor-specific CTL were consistently more effective than PSA or telomerase reverse transcriptase CTL to lyse tumor targets, suggesting the superiority of the polyclonal response. Although tumor RNA-transfected DC stimulated CTL, which recognized not only tumor but also self-Ags expressed by benign prostate tissue, these cross-reactive CTL were exclusively specific for the PSA, indicating an immunodominant role of PSA in the prostate cancer-specific immune response. Our data suggest that tumor RNA-transfected DC may represent a broadly applicable, potentially clinically effective vaccine strategy for prostate cancer patients, which is not limited by tumor tissue availability for Ag preparation and may minimize the risk of clonal tumor escape.
This article has been cited by other articles:
|
|
 |
|
  J. Dannull, D.-T. Lesher, R. Holzknecht, W. Qi, G. Hanna, H. Seigler, D. S. Tyler, and S. K. Pruitt Immunoproteasome down-modulation enhances the ability of dendritic cells to stimulate antitumor immunity Blood, December 15, 2007; 110(13): 4341 - 4350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Landi, L. A. Babiuk, and S. van Drunen Littel-van den Hurk High transfection efficiency, gene expression, and viability of monocyte-derived human dendritic cells after nonviral gene transfer J. Leukoc. Biol., October 1, 2007; 82(4): 849 - 860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. P. Tarassoff, P. M. Arlen, and J. L. Gulley Therapeutic vaccines for prostate cancer. Oncologist, May 1, 2006; 11(5): 451 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Elkord, P. E. Williams, H. Kynaston, and A. W. Rowbottom Differential CTLs specific for prostate-specific antigen in healthy donors and patients with prostate cancer Int. Immunol., October 1, 2005; 17(10): 1315 - 1325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nencioni and P. Brossart Cellular Immunotherapy with Dendritic Cells in Cancer: Current Status Stem Cells, July 1, 2004; 22(4): 501 - 513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Cisco, Z. Abdel-Wahab, J. Dannull, S. Nair, D. S. Tyler, E. Gilboa, J. Vieweg, Y. Daaka, and S. K. Pruitt Induction of Human Dendritic Cell Maturation Using Transfection with RNA Encoding a Dominant Positive Toll-Like Receptor 4 J. Immunol., June 1, 2004; 172(11): 7162 - 7168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Crozat and B. Beutler TLR7: A new sensor of viral infection PNAS, May 4, 2004; 101(18): 6835 - 6836. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kariko, H. Ni, J. Capodici, M. Lamphier, and D. Weissman mRNA Is an Endogenous Ligand for Toll-like Receptor 3 J. Biol. Chem., March 26, 2004; 279(13): 12542 - 12550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Coughlin, B. A. Vance, S. A. Grupp, and R. H. Vonderheide RNA-transfected CD40-activated B cells induce functional T-cell responses against viral and tumor antigen targets: implications for pediatric immunotherapy Blood, March 15, 2004; 103(6): 2046 - 2054. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Satoh, T. Saika, S. Ebara, N. Kusaka, T. L. Timme, G. Yang, J. Wang, V. Mouraviev, G. Cao, E. M. A. Fattah, et al. Macrophages Transduced with an Adenoviral Vector Expressing Interleukin 12 Suppress Tumor Growth and Metastasis in a Preclinical Metastatic Prostate Cancer Model Cancer Res., November 15, 2003; 63(22): 7853 - 7860. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Muller, F. Grunebach, A. Nencioni, and P. Brossart Transfection of Dendritic Cells with RNA Induces CD4- and CD8-Mediated T Cell Immunity Against Breast Carcinomas and Reveals the Immunodominance of Presented T Cell Epitopes J. Immunol., June 15, 2003; 170(12): 5892 - 5896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Su, J. Dannull, A. Heiser, D. Yancey, S. Pruitt, J. Madden, D. Coleman, D. Niedzwiecki, E. Gilboa, and J. Vieweg Immunological and Clinical Responses in Metastatic Renal Cancer Patients Vaccinated with Tumor RNA-transfected Dendritic Cells Cancer Res., May 1, 2003; 63(9): 2127 - 2133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Milazzo, V. L. Reichardt, M. R. Muller, F. Grunebach, and P. Brossart Induction of myeloma-specific cytotoxic T cells using dendritic cells transfected with tumor-derived RNA Blood, February 1, 2003; 101(3): 977 - 982. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. D. Davis, M. Jefford, P. Parente, and J. Cebon Rational approaches to human cancer immunotherapy J. Leukoc. Biol., January 1, 2003; 73(1): 3 - 29. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
