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Citations to this article

Tumor immunity and autoimmunity induced by immunization with homologous DNA.
L W Weber, … , J J Lewis, A N Houghton
L W Weber, … , J J Lewis, A N Houghton
Published September 15, 1998
Citation Information: J Clin Invest. 1998;102(6):1258-1264. https://doi.org/10.1172/JCI4004.
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Tumor immunity and autoimmunity induced by immunization with homologous DNA.

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Abstract

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.

Authors

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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M Mincheff, S Zoubak, I Altankova, S Tchakarov, Y Makogonenko, C Botev, I Ignatova, R Dimitrov, K Madarzhieva, M Hammett, Y Pomakov, H Meryman, T Lissitchkov
Cancer Gene Therapy 2003
Immunity to melanoma: unraveling the relation of tumor immunity and autoimmunity
T Ramirez-Montagut, MJ Turk, JD Wolchok, JA Guevara-Patino, AN Houghton
Oncogene 2003
CTLA-4 Blockade Enhances the Therapeutic Effect of an Attenuated Poxvirus Vaccine Targeting p53 in an Established Murine Tumor Model
J Espenschied, J Lamont, J Longmate, S Pendas, Z Wang, DJ Diamond, JD Ellenhorn
Journal of immunology (Baltimore, Md. : 1950) 2003
A Single Heteroclitic Epitope Determines Cancer Immunity After Xenogeneic DNA Immunization Against a Tumor Differentiation Antigen
JS Gold, CR Ferrone, JA Guevara-Patiño, WG Hawkins, R Dyall, ME Engelhorn, JD Wolchok, JJ Lewis, AN Houghton
Journal of immunology (Baltimore, Md. : 1950) 2003
Multiple pathways to tumor immunity and concomitant autoimmunity
MJ Turk, JD Wolchok, JA Guevara-Patino, SM Goldberg, AN Houghton
Immunological Reviews 2002
DNA-based immunotherapy: potential for treatment of chronic viral hepatitis?
S Beckebaum, VR Cicinnati, G Gerken
Reviews in Medical Virology 2002
Alphavirus-based DNA vaccine breaks immunological tolerance by activating innate antiviral pathways
WW Leitner, LN Hwang, MJ deVeer, A Zhou, RH Silverman, BR Williams, TW Dubensky, H Ying, NP Restifo
Nature Medicine 2002
Encyclopedia of Cancer
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
DNA vaccination with AFP-encoding plasmid DNA prevents growth of subcutaneous AFP-expressing tumors and does not interfere with liver regeneration in mice.
Hanke P, Serwe M, Dombrowski F, Sauerbruch T, Caselmann WH
Cancer gene therapy 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

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