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

"Self" melanocyte differentiation antigens are potential targets for specif ic melanoma immunotherapy. Vaccination against murine tyrosinase-related pr otein (TRP)-1/gp75 was shown recently to cause melanoma rejection, which wa s accompanied by autoimmune skin depigmentation (vitiligo), To further expl ore the linkage between immunotherapy and autoimmunity, we studied the resp onse to vaccination with a related antigen, TRP-2, i.m. inoculation of plas mid DNA encoding murine trp-2 elicited antigen-specific CTLs that recognize d the B16 mouse melanoma and protected the mice from challenge with tumor c ells. Furthermore, mice bearing established s.c. B16 melanomas rejected the tumor upon vaccination with a recombinant vaccinia virus encoding trp-2, D epletion experiments showed that CD8(+) lymphocytes and natural killer cell s were crucial for the antitumor activity of the trp-2-encoding vaccines, M ice that rejected the tumor did not develop generalized vitiligo, indicatin g that protective immunity can be achieved in the absence of widespread aut oimmune aggression.