Abstract 5423: Identification of immunotargets in Hedgehog medulloblastoma for immunotherapy

Abstract

Abstract Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Although approximately 75% of patients survive with current therapies, the associated complications drastically affect their quality of life, including severe neurological impairment and secondary cancers. Approximately 30% of MB cases exhibit activated hedgehog signaling pathway (HH-MB). Recent clinical trials using small molecular HH inhibitors exhibit promising results. Unfortunately, there are also indications of high rates of resistance and relapses, affirming the pressing need to develop complimentary therapies. Although immunotherapy has previously been proposed to treat MB, unique antigens are rare and monoclonal antibody therapies may not ensure tumor cytotoxicity, without additional adjuvants and associated severe side effects. However, recent successful developments of various cancer immunotherapies, especially the chimeric antigen receptor modified T-cell therapy, have rekindled interest in MB immunotherapies. To address the heterogeneity of MB and to develop a precision immunotherapy, we propose to identify uniquely or differentially overexpressed cell surface proteins in HH-MB, using human MB microarray and RNA-Seq data. Our preliminary studies have identified 39 potential candidates that are differentially expressed in HH-MB. We are currently confirming the presence and cellular localization of these candidate proteins using human MB tissue microarrays. This work is supported by NIH (T32 HL07915 [GST]) and Stand Up To Cancer - St. Baldrick's Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT1113). Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. Citation Format: Grace S. Tan, Tom Curran. Identification of immunotargets in Hedgehog medulloblastoma for immunotherapy. [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 5423. doi:10.1158/1538-7445.AM2015-5423