Anti-Tyrosinase Antibodies participate in the immune-response to vaccination with antiidiotypic antibodies mimicking the the High-Molecular-Weight-Melanoma-Associated-Antigen

Seven patients with metastatic melanoma were vaccinated with anti-idiotypic monoclonal antibody (mAb) MK2-23 which mimics the high-molecular-weight melanoma-associated antigen (HMW MAA), Sera samples were assayed for anti-anti-idiotypic antibodies, by Ab1-Ab2 complex inhibition test, for anti-Bls epitope antibodies, which are a heterogeneous group against various antigens presented on B16 melanoma cells and for anti-tyrosinase antibodies, which are specific against tyrosinase. Our results pointed to the participation of anti-tyrosinase antibodies in the immune response to vaccination by antiidiotypic antibodies mimicking the HMW MAA. The antityrosinase antibody kinetic curves presented an initial increase in titres in five cases followed by decreasing titres; in two cases a constant decrease was noted. The inhibition assay demonstrated an increasing percentage of inhibition (range 17-100%) within 100-400 days of treatment, The titre of the anti-tyrosinase antibodies increased following the vaccination, then decreased - probably due to absorption of the antibodies to melanoma cells and normal melanocytes. A positive slope in the percentage of inhibition was roughly associated with a negative slope of anti-tyrosinase antibodies. In one case, a long-standing complete clinical response was accompanied by development of melanoma-associated hypopigmentation. Anti-ale epitope antibodies had no role in the response to vaccination, The development of anti-tyrosinase antibodies in response to vaccination by anti-idiotypic antibodies mimicking another antigen may be explained by induction of non-specific polyclonal B lymphocytes activation, a well-recognized phenomenon in autoimmune disorders, While in autoimmune diseases the production of a second autoantibody may aggravate the course, in melanoma it may contribute to the regression of the disease in some patients.