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December 8, 2025BloodOpen Access

In Vivo clonal dynamics of alloreactive CAR T cells reveal mechanisms limiting gvhd risk following allogeneic CAR T cell therapy

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Authors

JKJames N. Kochenderfer

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Overview

Observational study shows anti-tumor activity of CAR T cells in B-cell malignancies, indicating limited GvHD risk post-alloHSCT.

Key Points

  • This study investigates the mechanisms behind GvHD risk following allogeneic CAR T cell therapy in patients with B-cell malignancies.
  • Identified 20 patients with relapsed or refractory B-cell malignancies post-alloHSCT treated with allogeneic CD19 CAR T cells.
  • Developed a cell-based platform to expand alloreactive T cells from donor PBMCs, engineered with a 28z CD19 CAR construct.
  • Used single-cell TCR and RNA sequencing for profiling alloreactive CAR T cell clones over time.
  • No new cases of acute GvHD were observed post-CAR T cell infusion in previously affected patients.
  • Alloreactive CAR T cells demonstrated potent anti-tumor activity while maintaining reduced effector function.
  • CAR engagement impaired recognition of TCR targets, suggesting altered signaling pathways.

Cite This Study

James N. Kochenderfer (2025) studied this question.

synapsesocial.com/papers/693624d44fa91c937236d032https://doi.org/10.1182/blood-2025-105
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