ATRT-24. CELL SURFACE PROTEOME ANALYSIS OF ATRT IDENTIFIES TARGETS FOR IMMUNOTHERAPY

Abstract

Atypical teratoid rhabdoid tumor (ATRT) is a rare and fast-growing childhood tumor of the brain and spinal cord. While the recent advances in DNA and RNA sequencing have given deep insights into the biology of cancer, about 90% of ATRTs harbor a single deletion which leads to uncontrolled tumor growth. The lack of targetable genetic abnormalities in ATRT makes it a tough target for therapy and hence radical new approaches are required to develop a treatment. In many cases, the gene expression profile alone DOES NOT represent the presence of the gene product on the surface and cannot detect post-translational modifications such as the addition of sugars which are essential for the interaction of surface proteins with the tumor microenvironment. The ability to escape from surveillance by the immune system is regarded as one of the essential hallmarks of cancer cells. Here we carried out a comprehensive unbiased large-scale surface receptor profiling using high throughput multicolor flow cytometry on surgically resected ATRT patient samples, primary ATRT cell lines, and patient-derived xenograft models. By multiplexing primary samples with antibodies for CD31, CD45, CD11b, CCR2, Cx3cr1, and CD4, and CD8 we eliminated endothelial and immune cells from analysis while also identifying immune populations within the tumor. We identified increased surface expression of CD44, CD146, CD59, CD151, and CD276. These were validated in our screening of primary tumor samples. A combination of CAR-T cell and function-blocking monoclonal antibody approaches have been tested to verify the proof of principle of this approach.