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December 8, 2025BloodOpen Access

Enhanced VLA4-dependent endothelial cell adhesion underpins the higher efficacy of CAR-iNKT over CAR-T cells in limiting leptomeningeal acute leukemia

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Authors

KKKlesti KaraxhukuBLBryan LyeCHChristina Halsey

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Overview

Pre-clinical data shows CAR-iNKT cells outperform CD19-targeting CAR-T cells in reducing leukemia burdens in a blood brain barrier model, suggesting improved immunotherapy options.

Key Points

  • To compare the efficacy of CAR-iNKT cells to CAR-T cells in treating leptomeningeal leukemia, focusing on adhesion mechanisms.
  • Investigated VLA-4 expression on CAR-iNKT and CAR-T cells through transcriptome analysis and flow cytometry.
  • Assessed adhesion capacities of these cells to VCAM-1 under static and shear stress conditions.
  • Utilized a B-ALL xenograft model in NSG mice to evaluate in vivo treatment effectiveness.
  • CAR-iNKT cells showed higher cytotoxic activity than CAR-T cells against leukemia cell lines.
  • VLA-4 expression was significantly higher in CAR-iNKT cells compared to CAR-T cells.
  • Treatment with CAR-iNKT cells significantly reduced leukemia burden in the meninges more effectively than CAR-T cells.

Cite This Study

Karaxhuku et al. (2025) studied this question.

synapsesocial.com/papers/69362f604fa91c937236dd32https://doi.org/10.1182/blood-2025-262
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Also Consider

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

  1. 1Off-the-shelf dual CAR-iNKT cell immunotherapy eradicates medullary and leptomeningeal high-risk KMT2A-rearranged leukemia2025 · 9 citations
  2. 2Targeting CD117 with engineered invariant natural killer T cells (iNKT Cells) as a novel approach for acute myeloid leukemia treatment2025
  3. 3Abstract 1332: Allogeneic CD19-directed CAR-iNKT cells and their phenotypic subsets for the treatment of CD19+ hematological malignancies2024
  4. 4Enhancing iNKT cell immunotherapy through the integration of optimized CAR endodomains and iNKT engagers2026
  5. 5CD19-CAR-iNKT cells transactivate NK cells and reduce alloreactivity2024 · 4 citations