ANTI-TYROSINASE ANTIBODIES PARTICIPATE IN THE IMMUNE-RESPONSE TO VACCINATION WITH ANTIIDIOTYPIC ANTIBODIES MIMICKING THE HIGH-MOLECULAR-WEIGHT MELANOMA-ASSOCIATED ANTIGEN

Seven patients with metastatic melanoma were vaccinated with anti-idio typic monoclonal antibody (mAb) MK2-23 which mimics the high-molecular -weight melanoma-associated antigen (HMW MAA), Sera samples were assay ed for anti-anti-idiotypic antibodies, by Ab1-Ab2 complex inhibition t est, 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 resu lts pointed to the participation of anti-tyrosinase antibodies in the immune response to vaccination by antiidiotypic antibodies mimicking t he HMW MAA. The antityrosinase antibody kinetic curves presented an in itial increase in titres in five cases followed by decreasing titres; in two cases a constant decrease was noted. The inhibition assay demon strated 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 associa ted with a negative slope of anti-tyrosinase antibodies. In one case, a long-standing complete clinical response was accompanied by developm ent of melanoma-associated hypopigmentation. Anti-ale epitope antibodi es had no role in the response to vaccination, The development of anti -tyrosinase antibodies in response to vaccination by anti-idiotypic an tibodies mimicking another antigen may be explained by induction of no n-specific polyclonal B lymphocytes activation, a well-recognized phen omenon in autoimmune disorders, While in autoimmune diseases the produ ction of a second autoantibody may aggravate the course, in melanoma i t may contribute to the regression of the disease in some patients.