Anti-tyrosinase antibodies participate in the immune response to vaccination with anti-idiotypic antibodies mimicking 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-B16 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 anti-idiotypic antibodies mimicking the HMW MAA. The anti-tyrosinase 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-B16 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Baharav
E
E
Research Institute, Beilinson Medical Centre, Petach Tiqvah, Israel.
Merimsky
O
O
Altomonte
M
M
Shoenfeld
Y
Y
Pavlovic
M
M
Maio
M
M
Ferrone
S
S
Fishman
P
P
D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000097:blood*; D000951:Antigens, Neoplasm; D000939:Epitopes; D006801:Humans; D007167:Immunotherapy; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D058950:Melanoma-Specific Antigens; D014442:Monophenol Monooxygenase / Q000276:immunology*; D009363:Neoplasm Proteins / Q000276:immunology*; D014611:Vaccination
D000888:Antibodies, Anti-Idiotypic; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000939:Epitopes; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D014442:Monophenol Monooxygenase