Genetic vaccination with "self" tyrosinase-related protein 2 causes melanoma eradication but not vitiligo. NLM AIDSLINE Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

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Genetic vaccination with "self" tyrosinase-related protein 2 causes melanoma eradication but not vitiligo.

Cancer Res. 2000 Jan 15;60(2):253-8. Unique Identifier : AIDSLINE MED/20129032
Bronte V; Apolloni E; Ronca R; Zamboni P; Overwijk WW; Surman DR; Restifo NP; Zanovello P; Department of Oncology and Surgical Sciences, University of; Padova, Italy. vbronte@ux1.unipd.it


Abstract: "Self" melanocyte differentiation antigens are potential targets for specific melanoma immunotherapy. Vaccination against murine tyrosinase-related protein (TRP)-1/gp75 was shown recently to cause melanoma rejection, which was accompanied by autoimmune skin depigmentation (vitiligo). To further explore the linkage between immunotherapy and autoimmunity, we studied the response to vaccination with a related antigen, TRP-2. i.m. inoculation of plasmid DNA encoding murine trp-2 elicited antigen-specific CTLs that recognized the B16 mouse melanoma and protected the mice from challenge with tumor cells. Furthermore, mice bearing established s.c. B16 melanomas rejected the tumor upon vaccination with a recombinant vaccinia virus encoding trp-2. Depletion experiments showed that CD8+ lymphocytes and natural killer cells were crucial for the antitumor activity of the trp-2-encoding vaccines. Mice that rejected the tumor did not develop generalized vitiligo, indicating that protective immunity can be achieved in the absence of widespread autoimmune aggression.


Keywords: JOURNAL ARTICLE Animal Cancer Vaccines/TOXICITY/*THERAPEUTIC USE CD8-Positive T-Lymphocytes/IMMUNOLOGY Interferon Type I/*IMMUNOLOGY Intramolecular Oxidoreductases/*IMMUNOLOGY Killer Cells, Natural/IMMUNOLOGY Lymphocyte Culture Test, Mixed Lymphocyte Depletion Melanoma, Experimental/*IMMUNOLOGY/*THERAPY Mice Mice, Inbred BALB C Mice, Inbred C57BL Peptides/CHEMISTRY/IMMUNOLOGY Pregnancy Proteins/*IMMUNOLOGY Support, Non-U.S. Gov't Vaccines, Synthetic/TOXICITY/*THERAPEUTIC USE Vitiligo/ETIOLOGY/*IMMUNOLOGYKWDjournalarticleanimalcancervaccines/toxicity/KWDtherapeuticusecd8-positivet-lymphocytes/immunologyinterferontypei/KWDimmunologyintramolecularoxidoreductases/KWDimmunologykillercells,natural/immunologylymphocyteculturetest,mixedlymphocytedepletionmelanoma,experimental/KWDimmunology/KWDtherapymicemice,inbredbalbcmice,inbredc57blpeptides/chemistry/immunologypregnancyproteins/KWDimmunologysupport,non-uKWDsKWDgov'tvaccines,synthetic/toxicity/KWDtherapeuticusevitiligo/etiology/KWDimmunology
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