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• W2012201322 abstract "Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DCTransformation of pigment producing melanocytes into melanoma is a complex multi-step process involving the generation and/or over expression of various immunotherapeutic antigens. Several of these melanoma associated antigens (MAAs) are directly involved in melanin biosynthesis and melanosome biogenesis. The precise contribution of proteins involved in melanin synthesis to the MAA associated immune response is poorly understood. To this end, we have developed primary cell lines from human patients and xenograft models to analyze melanin synthesis and antigen expression. In vitro, from the perspective of melanin production, these primary cell lines express essential proteins associated with melanin synthesis, namely tyrosinase, Trp-1, Trp-2, and gp100, all of which are immunotherapeutic targets in melanoma. When grafted in nude mice, these cell lines were capable of producing solid pigmented tumors in vivo. However, three out of the five cell lines that produced melanin in vivo failed to produce melanin in vitro, even when cultured with supplementation of either α-melanocyte stimulating hormone (MSH), basic fibroblast growth factor (bFGF), or matrigel. Despite expression of tyrosinase, Trp-1, Trp-2, and gp100, two of the five cell lines failed to grow in nude mice or produce melanin in vitro. These patient derived primary cells and xenografts were also analyzed for expression of various other significant MAAs, which included MART-1 (Melan-A), MAGE-A1, and NY-ESO-1 as well as antigens not classified as MAAs but essential for tumor progression such as CD71 (transferring receptor) and CD146 (MCAM or melanoma cell adhesion molecule). All of the antigens analyzed in our cell lines, such as gp100, NY-ESO-1, MART-1, MAGE-A1, have been the targets of clinical trials but our results clearly indicate that these antigens are differentially expressed by our primary melanoma cells. Therefore, we believe that in order to develop a clinically effective immunotherapeutic vaccine, multiple cell lines expressing a combination of melano-specific antigens and a repertoire of MAAs that allows for minimal immune evasion may be necessary. To this end, we are exploring a vaccinia virus antigen retrieval technology, which incorporates multiple primary cell lines to develop such a pan-antigen melanoma vaccine.Citation Format: Robert Suriano, Andrea L. George, Shilpi Rajoria, Jan Geliebter, Raj K. Tiwari, Marc Wallack. Patient-derived primary melanoma cells that differentially express melano-specific antigens as a model for vaccines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2829. doi:10.1158/1538-7445.AM2013-2829" @default.
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• W2012201322 date "2013-04-15" @default.
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• W2012201322 title "Abstract 2829: Patient-derived primary melanoma cells that differentially express melano-specific antigens as a model for vaccines." @default.
• W2012201322 doi "https://doi.org/10.1158/1538-7445.am2013-2829" @default.
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