ANTIBODY-RESPONSES TO MELANOMA MELANOCYTE AUTOANTIGENS IN MELANOMA PATIENTS/

Melanogenesis-related proteins play important roles in melanin synthes is and antigenicity of melanomas. Identification of highly expressed m elanoma-associated antigens (MAA) that are immunogenic in humans will provide potential targets for cancer vaccines. Melanogenesis-related p roteins have been shown to be MAA. Autoantibody responses to these MAA have been shown to react with melanoma cells and melanocytes, and sug gested to play a role in controlling melanoma progression. To assess a ntibody responses to potential melanoma/melanocyte autoantigens, the o pen-reading frame sequences of tyrosinase, tyrosinase-related protein (TRP)-1, TRP-2, and melanoma-associated glycoprotein antigen family (g p100/pmel17) genes were cloned and expressed as recombinant proteins i n E. coli. Purified recombinant antigens were employed to detect antib odies in sera of melanoma patients and normal healthy donors. By affin ity enzyme-linked immunosorbent assay and western blotting, all recomb inant antigens were shown to be antigenic. The main subclass of antibo dy response to these antigens was IgG. Most importantly this study dem onstrated anti-TRP-2 and anti-gp100/pmel17 IgG responses in melanoma p atients. Only one of 23 normal donors had an antibody response to the antigens tested. MAA-specific IgG antibodies in sera were assessed in melanoma patients (n = 23) pre- and post-polyvalent melanoma cell vacc ine treatment. Polyvalent melanoma cell vaccine treatment enhanced ant i-MAA antibody responses; however, only anti-TRP-2 and anti-gp100/pmel 17 antibody response was enhanced. These studies suggest that four mel anogenesis-related proteins are autoimmunogenic and can be used as pot ential targets for active-specific immunotherapy.