Structural surfaceomics reveals an AML-specific conformation of integrin β₂ as a CAR T cellular therapy target.

ABSTRACT: Safely expanding indications for cellular therapies has been challenging given a lack of highly cancer-specific surface markers. Here we explore the hypothesis that tumor cells express cancer-specific surface protein conformations that are invisible to standard target discovery pipelines evaluating gene or protein expression, and these conformations can be identified and immunotherapeutically targeted. We term this strategy integrating cross-linking mass spectrometry with glycoprotein surface capture 'structural surfaceomics'. As a proof of principle, we apply this technology to acute myeloid leukemia (AML), a hematologic malignancy with dismal outcomes and no known optimal immunotherapy target. We identify the activated conformation of integrin β₂ as a structurally defined, wid

SUBMITTER: Mandal K 

PROVIDER: S-EPMC10663162 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature