Genetic vaccination with "self" tyrosinase-related protein 2 causes melanoma eradication but not vitiligo.
"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.
Bronte
V
V
Department of Oncology and Surgical Sciences, University of Padova, Italy. vbronte@ux1.unipd.it
Apolloni
E
E
Ronca
R
R
Zamboni
P
P
Overwijk
W W
WW
Surman
D R
DR
Restifo
N P
NP
Zanovello
P
P
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use* / Q000633:toxicity; D007370:Interferon Type I / Q000276:immunology*; D019746:Intramolecular Oxidoreductases / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D008546:Melanoma, Experimental / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D011257:Pregnancy Proteins / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000627:therapeutic use* / Q000633:toxicity; D014820:Vitiligo / Q000209:etiology / Q000276:immunology*
D019496:Cancer Vaccines; D007370:Interferon Type I; D010455:Peptides; D011257:Pregnancy Proteins; D014614:Vaccines, Synthetic; C020947:interferon tau; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase