The immune system can recognize self antigens expressed by cancer cells. Differentiation antigens are prototypes of these self antigens, being expressed by cancer cells and their normal cell counterparts. The tyrosinase family proteins are well characterized differentiation antigens recognized by antibodies and T cells of patients with melanoma. However, immune tolerance may prevent immunity directed against these antigens. Immunity to the brown locus protein, gp75/ tyrosinase-related protein-1, was investigated in a syngeneic mouse model. C57BL/6 mice, which are tolerant to gp75, generated autoantibodies against gp75 after immunization with DNA encoding human gp75 but not syngeneic mouse gp75. Priming with human gp75 DNA broke tolerance to mouse gp75. Immunity against mouse gp75 provided significant tumor protection. Manifestations of autoimmunity were observed, characterized by coat depigmentation. Rejection of tumor challenge required CD4(+) and NK1.1(+) cells and Fc receptor gamma-chain, but depigmentation did not require these components. Thus, immunization with homologous DNA broke tolerance against mouse gp75, possibly by providing help from CD4(+) T cells. Mechanisms required for tumor protection were not necessary for autoimmunity, demonstrating that tumor immunity can be uncoupled from autoimmune manifestations.
L W Weber, W B Bowne, J D Wolchok, R Srinivasan, J Qin, Y Moroi, R Clynes, P Song, J J Lewis, A N Houghton
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G Sgouros |
Encyclopedia of Cancer | 2002 |
Tumorimmunabwehr und Autoimmunitat: Erkenntnisse fur die Entwicklung moderner Melanomvakzinen aus tierexperimentellen Studien. Tumor immunity and autoimmunity: lessons for the development of modern melanome vaccines learned in murine models
T Tuting, G Reinhard |
H&G Zeitschrift fur Hautkrankheiten | 2002 |
Redundant and Alternative Roles for Activating Fc Receptors and Complement in an Antibody-Dependent Model of Autoimmune Vitiligo
J Trcka, Y Moroi, RA Clynes, SM Goldberg, A Bergtold, MA Perales, M Ma, CR Ferrone, MC Carroll, JV Ravetch, AN Houghton |
Immunity | 2002 |
Oral DNA vaccination: antigen uptake and presentation by dendritic cells elicits protective immunity
B Cochlovius, MJ Stassar, MW Schreurs, A Benner, GJ Adema |
Immunology Letters | 2002 |
The efficacy of genetic vaccination is dependent upon the nature of the vector system and antigen
JL Bramson, YH Wan |
Expert Opinion on Biological Therapy | 2002 |
Preclinical evaluation of gene transfer products: safety and immunological aspects
M Christ |
Toxicology | 2002 |
Xenogeneic DNA Immunization in Melanoma Models for Minimal Residual Disease
WG Hawkins, JS Gold, NE Blachere, WB Bowne, A Hoos, JJ Lewis, AN Houghton |
Journal of Surgical Research | 2002 |
Gene Therapy of Cancer
IV Lebedeva, CA Stein |
Gene Therapy of Cancer | 2002 |
Strategies to overcome immune ignorance and tolerance
MA Perales, NE Blachere, ME Engelhorn, CR Ferrone, JS Gold, PD Gregor, G Noffz, JD Wolchok, AN Houghton |
Seminars in Cancer Biology | 2002 |
Melanoma Vaccines
MA Perales, JD Wolchok |
Cancer Investigation | 2002 |
The Potential of DNA Vaccination against Tumor-Associated Antigens for Antitumor Therapy
K Haupt, M Roggendorf, K Mann |
Experimental biology and medicine (Maywood, N.J.) | 2002 |
DNA vaccination with AFP-encoding plasmid DNA prevents growth of subcutaneous AFP-expressing tumors and does not interfere with liver regeneration in mice
P Hanke, M Serwe, F Dombrowski, T Sauerbruch, WH Caselmann |
Cancer Gene Therapy | 2002 |
Melanoma
EC Borden |
Melanoma | 2002 |
Dendritic cell-based xenoantigen vaccination for prostate cancer immunotherapy
L Fong, D Brockstedt, C Benike, JK Breen, G Strang, CL Ruegg, EG Engleman |
Journal of immunology (Baltimore, Md. : 1950) | 2001 |
Immunogene therapy of tumors with vaccine based on Xenopus homologous vascular endothelial growth factor as a model antigen
YQ Wei, MJ Huang, L Yang, X Zhao, L Tian, Y Lu, JM Shu, CJ Lu, T Niu, B Kang, YQ Mao, F Liu, YJ Wen, S Lei, F Luo, LQ Zhou, F Peng, Y Jiang, JY Liu, H Zhou, QR Wang, QM He, F Xiao, YY Lou, XJ Xie, Q Li, Y Wu, ZY Ding, B Hu, M Hu, W Zhang |
Proceedings of the National Academy of Sciences | 2001 |
B16 as a mouse model for human melanoma
WW Overwijk, NP Restifo |
Current protocols in immunology / edited by John E. Coligan ... [et al.] | 2001 |
MHC Class II–Restricted Tumor Antigens Recognized by CD4+ T Cells: New Strategies for Cancer Vaccine Design
G Zeng |
Journal of Immunotherapy | 2001 |
Immunity against cancer: lessons learned from melanoma
AN Houghton, JS Gold, NE Blachere |
Current Opinion in Immunology | 2001 |
Vaccines for melanoma: translating basic immunology into new therapies
JD Wolchok, PO Livingston |
The Lancet Oncology | 2001 |
Metastatic lesions in the joint associated with acute inflammatory arthritis after dendritic cell immunotherapy for metastatic melanoma
R Thomas, J Padmanabha, M Chambers, S McFadyen, E Walpole, G Nielssen, M Smithers |
Melanoma Research | 2001 |
Autoimmune Aspects of Vitiligo
EH Kemp, EA Waterman, AP Weetman |
Autoimmunity | 2001 |
Autoimmune Melanocyte Destruction in Vitiligo
R Wijngaard, A Wankowicz-Kalinska, S Pals, J Weening, P Das |
Laboratory Investigation | 2001 |
Adenovirus-transduced dendritic cells stimulate cellular immunity to melanoma via a CD4+ T cell-dependent mechanism
J Steitz, J Brück, J Knop, T Tüting |
Gene Therapy | 2001 |
The Skin and Gene Therapy
UR Hengge, B Volc-Platzer |
2001 | |
Induction of a Cellular and Humoral Immune Response against Preprocalcitonin by Genetic Immunization: A Potential New Treatment for Medullary Thyroid Carcinoma*
K Haupt, F Siegel, M Lu, D Yang, G Hilken, K Mann, M Roggendorf, B Saller |
Endocrinology | 2001 |
Renal Cancer: Methods and Protocols
JH Mydlo |
2001 | |
Tyrosinase family proteins are antigens specific to Vogt-Koyanagi-Harada disease
K Yamaki, K Gocho, K Hayakawa, I Kondo, S Sakuragi |
Journal of immunology (Baltimore, Md. : 1950) | 2000 |
Autoimmunity and the immunotherapy of cancer: targeting the "self" to destroy the "other"
WW Overwijk, NP Restifo |
Critical reviews in immunology | 2000 |
Immunotherapy with dendritic cells directed against tumor antigens shared with normal host cells results in severe autoimmune disease
B Ludewig, AF Ochsenbein, B Odermatt, D Paulin, H Hengartner, RM Zinkernagel |
Journal of Experimental Medicine | 2000 |
Genetic vaccination with "self" tyrosinase-related protein 2 causes melanoma eradication but not vitiligo
V Bronte, E Apolloni, R Ronca, P Zamboni, WW Overwijk, DR Surman, NP Restifo, P Zanovello |
Cancer research | 2000 |
Amplification of T Cell-Mediated Immune Responses by Antibody-Cytokine Fusion Proteins
HN Lode, R Xiang, SD Gillies, RA Reisfeld |
Immunological Investigations | 2000 |
Costimulatory wars: the tumor menace
AA Hurwitz, ED Kwon, A Elsas |
Current Opinion in Immunology | 2000 |
Immunization with DNA coding for gp100 results in CD4+ T-cell independent antitumor immunity
WG Hawkins, JS Gold, R Dyall, JD Wolchok, A Hoos, WB Bowne, R Srinivasan, AN Houghton, JJ Lewis |
Surgery | 2000 |
Genetic immunization of mice with human tyrosinase-related protein 2: Implications for the immunotherapy of melanoma
J Steitz, J Br�ck, K Steinbrink, A Enk, J Knop, T T�ting |
International Journal of Cancer | 2000 |
Intracutaneous Genetic Immunization with Autologous Melanoma-Associated Antigen Pmel17/gp100 Induces T Cell-Mediated Tumor Protection In Vivo
SN Wagner, C Wagner, P Luhrs, TK Weimann, R Kutil, M Goos, G Stingl, A Schneeberger |
Journal of Investigative Dermatology | 2000 |
Immunization of ovarian cancer patients with a synthetic Lewisy-protein conjugate vaccine: A phase 1 trial
PJ Sabbatini, V Kudryashov, G Ragupathi, SJ Danishefsky, PO Livingston, W Bornmann, M Spassova, A Zatorski, D Spriggs, C Aghajanian, S Soignet, M Peyton, C O'Flaherty, J Curtin, KO Lloyd |
International Journal of Cancer | 2000 |
Immunotherapy with Dendritic Cells Directed against Tumor Antigens Shared with Normal Host Cells Results in Severe Autoimmune Disease
B Ludewig, AF Ochsenbein, B Odermatt, D Paulin, H Hengartner, RM Zinkernagel |
Journal of Experimental Medicine | 2000 |
Mouse alpha-fetoprotein-specific DNA-based immunotherapy of hepatocellular carcinoma leads to tumor regression in mice
CF Grimm, D Ortmann, L Mohr, S Michalak, TU Krohne, S Meckel, S Eisele, J Encke, HE Blum, M Geissler |
Gastroenterology | 2000 |
Evaluation of CD8(+) T-cell frequencies by the Elispot assay in healthy individuals and in patients with metastatic melanoma immunized with tyrosinase peptide
JJ Lewis, S Janetzki, S Schaed, KS Panageas, S Wang, L Williams, M Meyers, L Butterworth, PO Livingston, PB Chapman, AN Houghton |
International Journal of Cancer | 2000 |
IL-12 plasmid-enhanced DNA vaccination against carcinoembryonic antigen (CEA) studied in immune-gene knockout mice
K Song, Y Chang, GJ Prud'homme |
Gene Therapy | 2000 |
Transfusion Medicine: New Clinical Applications of Cellular Immunotherapy
M Brenner, C Rossig, U Sili, JW Young, E Goulmy |
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | 2000 |
Identification of CD4 + T Cell Epitopes from NY-ESO-1 Presented by HLA-DR Molecules
G Zeng, CE Touloukian, X Wang, NP Restifo, SA Rosenberg, RF Wang |
Journal of immunology (Baltimore, Md. : 1950) | 2000 |
Divergent Roles for CD4 + T Cells in the Priming and Effector/Memory Phases of Adoptive Immunotherapy
HM Hu, H Winter, WJ Urba, BA Fox |
Journal of immunology (Baltimore, Md. : 1950) | 2000 |
Tumor-targeted IL-2 amplifies T cell-mediated immune response induced by gene therapy with single-chain IL-12
HN Lode, R Xiang, SR Duncan, AN Theofilopoulos, SD Gillies, RA Reisfeld |
Proceedings of the National Academy of Sciences | 1999 |
Coupling and uncoupling of tumor immunity and autoimmunity
WB Bowne, R Srinivasan, JD Wolchok, WG Hawkins, NE Blachere, R Dyall, JJ Lewis, AN Houghton |
Journal of Experimental Medicine | 1999 |
Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation
A Elsas, AA Hurwitz, JP Allison |
Journal of Experimental Medicine | 1999 |
Human tumor antigens for cancer vaccine development
RF Wang, SA Rosenberg |
Immunological Reviews | 1999 |
Autoaggression and tumor rejection: it takes more than self-specific T-cell activation
R Ganss, A Limmer, T Sacher, B Arnold, GJ Hammerling |
Immunological Reviews | 1999 |
Interpreting cancer vaccine clinical trials
G Dranoff |
The Journal of Gene Medicine | 1999 |
DNA vaccines for cancer therapy
HM Horton, SE Parker, MK Wloch, JA Norman |
Expert Opinion on Investigational Drugs | 1999 |
Coupling and Uncoupling of Tumor Immunity and Autoimmunity
WB Bowne, R Srinivasan, JD Wolchok, WG Hawkins, NE Blachere, R Dyall, JJ Lewis, AN Houghton |
Journal of Experimental Medicine | 1999 |
Combination Immunotherapy of B16 Melanoma Using Anti-Cytotoxic T Lymphocyte-Associated Antigen 4 (Ctla-4) and Granulocyte/Macrophage Colony-Stimulating Factor (Gm-Csf)-Producing Vaccines Induces Rejection of Subcutaneous and Metastatic Tumors Accompanied by Autoimmune Depigmentation
A Elsas, AA Hurwitz, JP Allison |
Journal of Experimental Medicine | 1999 |
High avidity CTLs for two self-antigens demonstrate superior in vitro and in vivo antitumor efficacy
WW Overwijk, DS Lee, DR Surman, KR Irvine, CE Touloukian, CC Chan, MW Carroll, B Moss, SA Rosenberg, NP Restifo |
Journal of immunology (Baltimore, Md. : 1950) | 1999 |
Vaccination with a recombinant vaccinia virus encoding a "self" antigen induces autoimmune vitiligo and tumor cell destruction in mice: requirement for CD4(+) T lymphocytes.
Overwijk WW, Lee DS, Surman DR, Irvine KR, Touloukian CE, Chan CC, Carroll MW, Moss B, Rosenberg SA, Restifo NP |
Proceedings of the National Academy of Sciences | 1999 |
DNA vaccines
JB Ulmer, JC Sadoff, MA Liu |
Current Opinion in Immunology | 1996 |