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Methods Mol Biol. 2020;2097:45-54. doi: 10.1007/978-1-0716-0203-4_2.

Identification of Cell Surface Targets for CAR T Cell Immunotherapy.

DeLucia DC1,2,3, Lee JK4,5,6.

Author information

1
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
2
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
3
Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
4
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. jklee5@fredhutch.org.
5
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. jklee5@fredhutch.org.
6
Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA. jklee5@fredhutch.org.

Abstract

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.

KEYWORDS:

CAR T cell; Cell surface antigens; Chimeric antigen receptor; Mass spectrometry; Proteomics; RNA sequencing; Transcriptomics

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