Abstract
Abstract Melanoma is a fast progressing tumor, which originates from melanocytes and it is known to be highly resistant to many therapies. Although it has been proven to be very immunogenic and a number of various melanoma associated antigens are well known, nevertheless, the immune response of the patients is often not able to fight back and eliminate all tumor cells. It has been recently shown that a new class of tumor antigens, called cancer-retina antigens (CRA), apart from being expressed in a healthy retina, can be expressed at the mRNA and protein level in melanoma. The aberrant expression of transducin, cGMP-phosphodiesterase 6 (PDE6), guanylyl cyclase, recoverin and arrestin have been detected in tumor cells of melanoma patients and in tumor-bearing mice. These antigens can elicit humoral and cellular immune responses. We aim to investigate if CRA could serve as potential target antigens for immunotherapy approaches against melanoma. Among these antigens, human PDE6 was selected and analyzed for its immunogenicity in normal C57BL/6 mice and in HLA-DRB1*0301tg mice. Human (xenogenic) PDE6 alpha has been cloned and used for DNA immunization of BL/6 and HLA transgenic mice. By IFN-γ ELISPOT assay employing synthetic peptide libraries, immunogenic peptides have been identified and CRA specific T cell epitopes were determined. Further on, PDE6-specific T cells lines will be generated and their therapeutic efficiency will be checked in transplantable tumor mouse models or in transgenic mice with spontaneous melanoma formation. In addition, peripheral blood mononuclear cells (PBMCs) from tumor patients will be analyzed for the presence of specific T cells against the epitopes identified in HLA-transgenic mice. These T cells will be expanded and tested for their reactivity against HLA-matched human melanoma cell lines in vitro. Finally, both established CRA-specific T-cell lines and synthetic polypeptides will be tested as vaccines in therapeutical and preventive settings in melanoma animal tumor models. Immunized animals will be monitored for any signs of autoimmune retinopathy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-126. doi:1538-7445.AM2012-LB-126
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