| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Immunology |
Department of Tumor Immunology, University Medical Center St. Radboud, Philips van Leydenlaan 25, 6525 EX Nijmegen [A. A. O. E., A. J. d. B., J. L. M. V., C. G. F., G. J. A.], Department of Immunohematology and Blood Bank, Leiden University Medical Centre, 2300 RC Leiden [T. v. H., R. O.], The Netherlands
Tyrosinase-related protein (TRP) 2 belongs to the melanocyte differentiation antigens and has been implicated as a target for immunotherapy of human as well as murine melanoma. In the current report, we explored the efficacy of nonmutated epitopes with differential binding affinity for MHC class I, derived from mouse TRP2 to induce CTL-mediated, tumor-reactive immunity in vivo within the established B16 melanoma model of C57BL/6 mice. The use of nonmutated TRP2-derived epitopes for vaccination provides a mouse model that closely mimics human melanoma without introduction of xenogeneic or otherwise foreign antigen. The results demonstrate that vaccination with TRP2 peptide-loaded bone marrow-derived dendritic cells (DCs) results in activation of high avidity TRP2-specific CTLs, displaying lytic activity against both B16 melanoma cells and normal melanocytes in vitro. In vivo, protective antitumor immunity against a lethal s.c. B16 challenge was observed upon DC-based vaccination in this fully autologous tumor model. The level of protective immunity positively correlated with the MHC class I binding capacity of the peptides used for vaccination. In contrast, within this autologous model, vaccination with TRP2 peptide in Freund’s adjuvant or TRP2-encoding plasmid DNA did not result in protective immunity against B16. Strikingly, despite the observed CTL-mediated melanocyte destruction in vitro, melanocyte destruction in vivo was sporadic and primarily restricted to minor depigmentation of the vaccination site. These results emphasize the potency of DC-based vaccines to induce immunity against autologous tumor-associated antigen and indicate that CTL-mediated antitumor immunity can proceed without development of adverse autoimmunity against normal tissue.
This article has been cited by other articles:
|
|
 |
|
  K. D. Pavelko, M. J. Hansen, and L. R. Pease CTL Activation Using the Natural Low-Affinity Epitope 222-229 from Tyrosinase-Related Protein 1 Leads to Tumor Rejection Cancer Res., April 1, 2009; 69(7): 3114 - 3120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Kochenderfer and R. E. Gress A Comparison and Critical Analysis of Preclinical Anticancer Vaccination Strategies Experimental Biology and Medicine, October 1, 2007; 232(9): 1130 - 1141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nair, D. Boczkowski, M. Fassnacht, D. Pisetsky, and E. Gilboa Vaccination against the Forkhead Family Transcription Factor Foxp3 Enhances Tumor Immunity Cancer Res., January 1, 2007; 67(1): 371 - 380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. M. Dirkx, M. G. A. oude Egbrink, J. Wagstaff, and A. W. Griffioen Monocyte/macrophage infiltration in tumors: modulators of angiogenesis J. Leukoc. Biol., December 1, 2006; 80(6): 1183 - 1196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Lee, M. Fassnacht, S. Nair, D. Boczkowski, and E. Gilboa Tumor Immunotherapy Targeting Fibroblast Activation Protein, a Product Expressed in Tumor-Associated Fibroblasts Cancer Res., December 1, 2005; 65(23): 11156 - 11163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Tacken, I. J. M. de Vries, K. Gijzen, B. Joosten, D. Wu, R. P. Rother, S. J. Faas, C. J. A. Punt, R. Torensma, G. J. Adema, et al. Effective induction of naive and recall T-cell responses by targeting antigen to human dendritic cells via a humanized anti-DC-SIGN antibody Blood, August 15, 2005; 106(4): 1278 - 1285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Ji, D. Gondek, and A. A. Hurwitz Provision of Granulocyte-Macrophage Colony-Stimulating Factor Converts an Autoimmune Response to a Self-Antigen into an Antitumor Response J. Immunol., August 1, 2005; 175(3): 1456 - 1463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Ossendorp, N. Fu, M. Camps, F. Granucci, S. J. P. Gobin, P. J. van den Elsen, D. Schuurhuis, G. J. Adema, G. B. Lipford, T. Chiba, et al. Differential Expression Regulation of the {alpha} and {beta} Subunits of the PA28 Proteasome Activator in Mature Dendritic Cells J. Immunol., June 15, 2005; 174(12): 7815 - 7822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hanada, K. Tanaka, Y. Matsumura, M. Yamauchi, H. Nishinakamura, H. Aburatani, R. Mashima, M. Kubo, T. Kobayashi, and A. Yoshimura Induction of Hyper Th1 Cell-Type Immune Responses by Dendritic Cells Lacking the Suppressor of Cytokine Signaling-1 Gene J. Immunol., April 1, 2005; 174(7): 4325 - 4332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Okano, M. Merad, K. Furumoto, and E. G. Engleman In Vivo Manipulation of Dendritic Cells Overcomes Tolerance to Unmodified Tumor-Associated Self Antigens and Induces Potent Antitumor Immunity J. Immunol., March 1, 2005; 174(5): 2645 - 2652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Prasad, K. J. Farrand, S. A. Matthews, J. H. Chang, R. S. McHugh, and F. Ronchese Dendritic Cells Loaded with Stressed Tumor Cells Elicit Long-Lasting Protective Tumor Immunity in Mice Depleted of CD4+CD25+ Regulatory T Cells J. Immunol., January 1, 2005; 174(1): 90 - 98. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lane, J. Leitch, X. Tan, J. Hadjati, J. L. Bramson, and Y. Wan Vaccination-Induced Autoimmune Vitiligo Is a Consequence of Secondary Trauma to the Skin Cancer Res., February 15, 2004; 64(4): 1509 - 1514. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-F. Wu, T.-M. Liu, Y.-C. Lin, H.-K. Sytwu, H.-F. Juan, S.-T. Chen, K.-L. Shen, S.-C. Hsi, and S.-L. Hsieh Immunomodulatory effect of decoy receptor 3 on the differentiation and function of bone marrow-derived dendritic cells in nonobese diabetic mice: from regulatory mechanism to clinical implication J. Leukoc. Biol., February 1, 2004; 75(2): 293 - 306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nair, C. McLaughlin, A. Weizer, Z. Su, D. Boczkowski, J. Dannull, J. Vieweg, and E. Gilboa Injection of Immature Dendritic Cells into Adjuvant-Treated Skin Obviates the Need for Ex Vivo Maturation J. Immunol., December 1, 2003; 171(11): 6275 - 6282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhao, D. Boczkowski, S. K. Nair, and E. Gilboa Inhibition of invariant chain expression in dendritic cells presenting endogenous antigens stimulates CD4+ T-cell responses and tumor immunity Blood, December 1, 2003; 102(12): 4137 - 4142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nair, D. Boczkowski, B. Moeller, M. Dewhirst, J. Vieweg, and E. Gilboa Synergy between tumor immunotherapy and antiangiogenic therapy Blood, August 1, 2003; 102(3): 964 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Davila, R. Kennedy, and E. Celis Generation of Antitumor Immunity by Cytotoxic T Lymphocyte Epitope Peptide Vaccination, CpG-oligodeoxynucleotide Adjuvant, and CTLA-4 Blockade Cancer Res., June 15, 2003; 63(12): 3281 - 3288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. M. Dirkx, M. G. A. oude Egbrink, M. J. E. Kuijpers, S. T. van der Niet, V. V. T. Heijnen, J. C. A. B.-t. Steege, J. Wagstaff, and A. W. Griffioen Tumor Angiogenesis Modulates Leukocyte-Vessel Wall Interactions in Vivo by Reducing Endothelial Adhesion Molecule Expression Cancer Res., May 1, 2003; 63(9): 2322 - 2329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Hodge, D. W. Grosenbach, W. M. Aarts, D. J. Poole, and J. Schlom Vaccine Therapy of Established Tumors in the Absence of Autoimmunity Clin. Cancer Res., May 1, 2003; 9(5): 1837 - 1849. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Samady, E. Costigliola, L. MacCormac, Y. McGrath, S. Cleverley, C. E. Lilley, J. Smith, D. S. Latchman, B. Chain, and R. S. Coffin Deletion of the Virion Host Shutoff Protein (vhs) from Herpes Simplex Virus (HSV) Relieves the Viral Block to Dendritic Cell Activation: Potential of vhs- HSV Vectors for Dendritic Cell-Mediated Immunotherapy J. Virol., March 15, 2003; 77(6): 3768 - 3776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Oh, J. W. Hodge, J. D. Ahlers, D. S. Burke, J. Schlom, and J. A. Berzofsky Selective Induction of High Avidity CTL by Altering the Balance of Signals from APC J. Immunol., March 1, 2003; 170(5): 2523 - 2530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kalat, Z. Kupcu, S. Schuller, D. Zalusky, M. Zehetner, W. Paster, and T. Schweighoffer In Vivo Plasmid Electroporation Induces Tumor Antigen-specific CD8+ T-Cell Responses and Delays Tumor Growth in a Syngeneic Mouse Melanoma Model Cancer Res., October 1, 2002; 62(19): 5489 - 5494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Paster, M. Kalat, M. Zehetner, and T. Schweighoffer Structural Elements of a Protein Antigen Determine Immunogenicity of the Embedded MHC Class I-Restricted T Cell Epitope J. Immunol., September 15, 2002; 169(6): 2937 - 2946. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. Mullins, T. N. J. Bullock, T. A. Colella, V. V. Robila, and V. H. Engelhard Immune Responses to the HLA-A*0201-Restricted Epitopes of Tyrosinase and Glycoprotein 100 Enable Control of Melanoma Outgrowth in HLA-A*0201-Transgenic Mice J. Immunol., November 1, 2001; 167(9): 4853 - 4860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P.M. Sutmuller, L. M. van Duivenvoorde, A. van Elsas, T. N.M. Schumacher, M. E. Wildenberg, J. P. Allison, R. E.M. Toes, R. Offringa, and C. J.M. Melief Synergism of Cytotoxic T Lymphocyte-associated Antigen 4 Blockade and Depletion of CD25+ Regulatory T Cells in Antitumor Therapy Reveals Alternative Pathways for Suppression of Autoreactive Cytotoxic T Lymphocyte Responses J. Exp. Med., September 17, 2001; 194(6): 823 - 832. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. van Elsas, R. P.M. Sutmuller, A. A. Hurwitz, J. Ziskin, J. Villasenor, J.-P. Medema, W. W. Overwijk, N. P. Restifo, C. J.M. Melief, R. Offringa, et al. Elucidating the Autoimmune and Antitumor Effector Mechanisms of a Treatment Based on Cytotoxic T Lymphocyte Antigen-4 Blockade in Combination with a B16 Melanoma Vaccine: Comparison of Prophylaxis and Therapy J. Exp. Med., August 20, 2001; 194(4): 481 - 490. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
