The abstract is read at the publisher; the summary is JClub's.
hAB2 CAR-T cells selectively eradicate CALRmut myeloproliferative neoplasm–sustaining stem cells in patient-derived tumor xenografts, eliminating all detectable MPN-propagating function in serial transplantation assays.
- Why it matters: MPN stem cells persist despite current therapies, and allogeneic HSCT is curative but non-selective, risking toxicity and death. A selective strategy requires MPN HSCs to display CALRmut at the cell surface in vivo.
- What they did: The study generated hAB2, a high-affinity CALRmut-specific humanized antibody, as the CAR binding domain and tested it in vitro and in vivo for surface CALRmut detection. It then used an MPN patient-derived tumor xenograft model to evaluate hAB2 CAR-T–mediated elimination of CALRmut MPN HSCs.
- The result: Functional murine and human MPN HSCs expressed surface CALRmut detected by AB2 in vitro and in vivo. In PDTX models, hAB2 CAR-T selectively eliminated CALRmut MPN HSCs while preserving co-existing normal human and host hematopoiesis, supporting transplant-free immunotherapy feasibility.
The findingWhy it mattersWhat they didThe result
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