Citations to this article
Citation Information: J Clin Invest. 1998;102(6):1258-1264. https://doi.org/10.1172/JCI4004.
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
Total citations by year
Citations to this article in year 2008 (7)
| Title and authors | Publication | Year |
|---|---|---|
|
Mechanisms of Immunization Against Cancer Using Chimeric Antigens
ME Engelhorn, JA Guevara-Patiño, T Merghoub, C Liu, CR Ferrone, GA Rizzuto, DH Cymerman, DN Posnett, AN Houghton, JD Wolchok |
Molecular Therapy | 2008 |
|
Improved tumor immunity using anti-tyrosinase related protein-1 monoclonal antibody combined with DNA vaccines in murine melanoma
YM Saenger, Y Li, KC Chiou, B Chan, G Rizzuto, SL Terzulli, T Merghoub, AN Houghton, JD Wolchok |
Cancer research | 2008 |
|
Dendritic cell based genetic immunization stimulates potent tumor protection dependent on CD8 CTL cells in the absence of autoimmunity
S Zhang, W Huang |
Journal of Cancer Research and Clinical Oncology | 2008 |
|
Induction of T cell-mediated immunity using a c-Myb DNA vaccine in a mouse model of colon cancer
BB Williams, M Wall, RY Miao, B Williams, I Bertoncello, MH Kershaw, T Mantamadiotis, M Haber, MD Norris, A Gautam, PK Darcy, RG Ramsay |
Cancer Immunology, Immunotherapy | 2008 |
|
Generation and characterization of transgenic mice expressing a T-cell receptor specific for the tumour-associated antigen MDM2
SA Xue, GM Bendle, A Holler, HJ Stauss |
Immunology | 2008 |
|
Phase I/II Study of GM-CSF DNA as an Adjuvant for a Multipeptide Cancer Vaccine in Patients With Advanced Melanoma
MA Perales, J Yuan, S Powel, HF Gallardo, TS Rasalan, C Gonzalez, G Manukian, J Wang, Y Zhang, PB Chapman, SE Krown, PO Livingston, S Ejadi, KS Panageas, ME Engelhorn, SL Terzulli, AN Houghton, JD Wolchok |
Molecular Therapy | 2008 |
|
Molecular Targeting in Oncology
HL Kaufman, S Wadler, K Antman |
2008 |
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