IMPLICATING A ROLE FOR IMMUNE RECOGNITION OF SELF IN TUMOR REJECTION - PASSIVE-IMMUNIZATION AGAINST THE BROWN LOCUS PROTEIN

The immune system can recognize differentiation antigens that are sele ctively expressed on malignant cells and their normal cell counterpart s. However, it is uncertain whether immunity to differentiation antige ns can effectively lead to tumor rejection. The mouse brown locus prot ein, gp75 or tyrosinase-related protein 1, is a melanocyte differentia tion antigen expressed by melanomas and normal melanocytes. The gp75 a ntigen is recognized by autoantibodies and autoreactive T cells in per sons with melanoma. To model autoimmunity against a melanocyte differe ntiation antigen, mouse antibodies against gp75 were passively transfe rred into tumor-bearing mice. Passive immunization with a mouse monocl onal antibody against gp75 induced protection and rejection of both su bcutaneous tumors and lung metastases in syngeneic C57BL/6 mice, inclu ding established tumors. Passive immunity produced coat color alterati ons but only in regenerating hairs. This system provides a model for a utoimmune vitiligo and shows that immune responses to melanocyte diffe rentiation antigens can influence mouse coat color. Immune recognition of a melanocyte differentiation antigen can reject tumors, providing a basis for targeting tissue autoantigens expressed on cancer.