Identification of Cell Surface Targets for CAR T Cell Immunotherapy
Immunotherapy has become a prominent approach for the treatment of cancer. Targeted killing of malignant cells by adoptive transfer of chimeric antigen receptor (CAR) T cells is a promising immunotherapy technique in oncology. However, the identification of cell surface antigens unique to tumor cells against which CAR T cells can be engineered has historically been challenging and not well documented in solid tumors. Here, we describe a generalized method to construct a cell subtype-specific surface antigen profile (i.e., surfaceome) from cell lines and identify high-confidence antigens as effective targets for CAR T cell therapy by integrating transcriptomics and cell surface proteomics. This method is widely applicable to all therapies utilizing CAR T cells, such as cancer, as well as infectious and autoimmune diseases.
KeywordsCell surface antigens Chimeric antigen receptor CAR T cell RNA sequencing Transcriptomics Proteomics Mass spectrometry
We thank the UCLA Technology Center for Genomics & Bioinformatics and the UCLA Proteomics Research Center for providing assistance with the workflows. This work was supported by the Department of Defense Prostate Cancer Research Program Physician Research Award (W81XWH-17-1-0129) and a Prostate Cancer Young Investigator Award to J.K.L.
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