SEROLOGICAL PROFILING OF MELANOMA PATIENTS AS A DIAGNOSTIC TOOL

Yale University, New Haven CT

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Abstract

Immune responses to autoantigens are prevalent in melanoma. Autoantibodies and tumor specific cytotoxic[unreadable] T-lymphocytes (CTL) have been identified, isolated and characterized. While these spontaneous immuneresponses[unreadable] are often insufficient to induce tumor regression, they can be harnessed for diagnosis, assesing[unreadable] prognosis, active immunotherapy, and selection of patients for immunotherapy. A major obstacle in[unreadable] achieving these goals has been the variability in patients' responses, as the experience so far is that only a[unreadable] fraction of patients share immune responses to the same antigens. Our preliminary results employing highdensity[unreadable] protein microarrays (ProtoArrays from Invitrogen) suggest that a great number of serological[unreadable] responses exist that have not been detected by prior methods. Our data confirm that a proteome-wide[unreadable] screen can reveal melanoma-associated serological profiles (antibodies and antigens) that can be used as[unreadable] the basis for a comprehensive, informative and clinically applicable screening test. We will therefore expand[unreadable] our interrogation of ProtoArrays composed of thousands of recombinant human proteins for serological[unreadable] immune- profiles in a global unbiased fashion. In Aim 1 we will employ the high-density Invitrogen human[unreadable] ProtoArrays to screen for serum autoantibodies and discover new antigens in patients with melanoma[unreadable] compared to patients with lung cancer and control healthy individuals. In Aim 2 we will validate the[unreadable] serological profiles with the ProtoArrays in a large number of melanoma patients with primary and metastatic[unreadable] disease. In Aim 3 we will assess the specificity of the antibodies and the presence of the antigens in serum,[unreadable] tumors and cells by performing Western blotting, reciprocal immunoprecipitation/immunoblotting analyses,[unreadable] sandwich immunoassays and immunohistochemistry. We will assess sensitivity, accuracy and reproducibility[unreadable] in discriminating between sera from patients and healthy individuals, and patients with different disease[unreadable] stages. The results from our studies will be the basis for the development of a serum immunome-profile test[unreadable] for diagnosis of melanoma. The test could also be developed to assess propensity to recur, responses to[unreadable] therapy, and to monitor disease progression. It will enable new therapeutic, diagnostic, and prognostic[unreadable] options, and assist in selection of patients for adjuvant therapy and vaccine therapies.[unreadable]