Abstract 4845: Microarray analysis of melanoma autologous tumor cell lines used as the source of tumor associated antigens in patient-specific dendritic cell immunotherapy phase II trial in patients with metastatic melanoma

Abstract

Abstract Melanoma cells that are proliferating and self-renewing in short-term cell culture, have the phenotypic and functional characteristics of tumor stem cells, and they express unique patient-specific neoantigens, as well as numerous common melanoma associated antigens. Patient-specific therapeutic vaccines, produced by Incubating autologous dendritic cells with autologous tumor cells from such cell lines (DC-TC), have yielded promising results in phase II trials in metastatic melanoma. In this study we examined the expression of genes on the tumor cell lines which had served as the sources of tumor associated antigens loaded onto autologous dendritic cells as part of a phase II trial in which there was an observed 5-year survival rate of 50%.[Dillman 2009] There was sufficient melanoma tumor cells to analyze for 50 of the 54 patients enrolled in the phase II trial. Microarray analysis was performed by Response Genetics, Inc. (Los Angeles) for 54,000 genes. The Excel data file was entered into an Affymetrix data processing algorithm using the R programming language. Gene ranking was performed using prediction analysis of microarrays.[Tibshirani 2002] Correlation with overall survival was done for 26 patients who survived 5 years or longer, and 24 patients who survived less than 5 years. Hierarchical clustering for over and under expression yielded 9 genes, VEPH1, ZNF280B, FGF13, ST6GALNAC3, QPCT, ZNF280B, BST, PBRM1 and C21orf91 which identified 11/11 patients who had a survival greater than 5 years, and 17/18 patients who died in less than 2 years. Using the top six genes, overall survival greater than 5 years was correctly predicted for 80.3% of patients, and survival less than 5 years was correctly predicted for 74.2% of patients. Gene array data obtained from self-renewing, proliferating, autologous tumor cells was prognostic for survival. It is unclear whether these genes are predictive of an effective immune response after repeated injections of a therapeutic dendritic cell-tumor cell vaccine. Citation Format: Andrew N. Cornforth, Gary Fogel, Denysha Carbonell, Robert O. Dillman. Microarray analysis of melanoma autologous tumor cell lines used as the source of tumor associated antigens in patient-specific dendritic cell immunotherapy phase II trial in patients with metastatic melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4845. doi:10.1158/1538-7445.AM2015-4845