Available online 8 April 2025, 102524

Mass spectrometry-based methods reveal AML-specific surface proteins without relying on predefined antibodies, offering unbiased target identification.

Structural surfaceomics identifies tumor-specific protein conformations, potentially improving the specificity of CAR T cells.

Integrating proteomics with transcriptomics refines target selection by excluding antigens expressed on healthy tissues.

AI-powered single-cell RNA sequencing enhances target discovery by analyzing gene expression at the individual cell level, improving specificity and minimizing potential on-target effects.

Surfaceomics integrating single-cell RNA sequencing and surface proteomic data identify a multitude of novel AML target antigens both as pan-AML and AML subtype markers.

Identifying safe and effective CAR T cell targets in acute myeloid leukemia (AML) is challenging due to the disease’s complexity and overlap with normal hematopoiesis. This review highlights advances in target discovery for AML, emphasizing innovative approaches. Structural surfaceomics identifies tumor-specific protein conformations, while AI-driven single-cell RNA sequencing integrates multi-source data to pinpoint optimal targets. Refined cell surface capture technology maps the AML surfaceome without relying on predefined antibodies. These strategies enhance CAR T cell specificity and minimize off-tumor effects, offering promising pathways for safer and more effective AML treatments and broader cancer therapies.

Chimeric antigen receptor

adoptive T cell therapy

acute myeloid leukemia

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© 2025 The Authors. Published by Elsevier Ltd.