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September 10, 2025BloodOpen Access

Off-the-shelf dual CAR-iNKT cell immunotherapy eradicates medullary and leptomeningeal high-risk KMT2A-rearranged leukemia

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Authors

HRHongwei RenChinese PLA General HospitalNENatalina ElliottUniversity of OxfordBLBryan LyeUNSW Sydney

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Implication

Observational analysis shows improved anti-leukemia activity in KMT2Ar-ALL infants, highlighting potential for dual-target immunotherapy.

Key Points

  • Bi-specific CAR-iNKT cells eradicate medullary and leptomeningeal leukemia effectively.
  • Compared to CAR-T, CD19-CD133 CAR-iNKT have a more potent anti-leukemia activity against KMT2Ar-ALL.
  • Mechanistically, engagement of NKG2D on CAR-iNKT enhances targeting even with downregulated antigens.
  • This novel approach can be adapted for other high-risk malignancies with challenging central nervous system involvement.

Cite This Study

Ren et al. (2025) studied this question.

synapsesocial.com/papers/68c188499b7b07f3a0611d77https://doi.org/10.1182/blood.2025029302
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Targeting CD117 with engineered invariant natural killer T cells (iNKT Cells) as a novel approach for acute myeloid leukemia treatment2025
  2. 2Enhanced VLA4-dependent endothelial cell adhesion underpins the higher efficacy of CAR-iNKT over CAR-T cells in limiting leptomeningeal acute leukemia2025
  3. 3Novel allogeneic BCMA CAR-expressing iNKT cells with PD1 deletion demonstrate superior tumor control in a multiple myeloma preclinical model2025
  4. 4Abstract 137: Harnessing allogeneic CAR-iNKT cells for next-generation treatments in oncology and autoimmunity.2026
  5. 5CD19-chimeric antigen receptor-invariant natural killer T cells transactivate NK cells and reduce alloreactivity2024 · 4 citations