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A hematopoietic stem cell shield for AML-directed immunotherapy

GSE317101 Homo sapiens Expression profiling by high throughput sequencing; Other 6 samples Submitted 2026/04/08 Platform GPL24676
Summary
One major challenge in the development of successful chimeric antigen receptor (CAR) T cells for patients with acute myeloid leukemia (AML) has been that most well-studied AML-associated antigens are also expressed on vital normal hematopoietic stem cells (HSCs) or mature myeloid cells. This challenge in optimal antigen selection leads to deleterious on-target toxicity, particularly in the context of CAR T cell persistence. CAR T cells targeting CD371, a type II transmembrane glycoprotein, have shown potent anti-leukemic activity in phase I trials to date; however, CD371 is wildly expressed throughout the normal myeloid compartment. Here we identify that CD371 is dispensable for normal human HSC and myeloid cell function, map the epitope of a CD371 CAR T cell currently in phase I trials, develop a base-editing strategy to shield normal hematopoiesis from CD371-directed immunotherapy, and describe an off-the-shelf approach to target AML while sparing normal hematopoiesis through the use of CD371 CAR T cells.
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Direct links to NCBI, no account and no request form: the whole study as GSE317101_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 6 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1405779 and SRA study SRP665017. Searching any of these in the dataset finder brings you back here.

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