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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

Investigating CAR T cell behaviors reduces graft-versus-host disease risk in patients with B-cell malignancies, suggesting safer therapies.

Key Points

  • This research aims to explore how alloreactive CAR T cells influence graft-versus-host disease risk in patients.
  • Identified 20 patients treated with allogeneic CD19 CAR T cells post-alloHSCT.
  • Developed a novel platform to display HLA molecules and expand alloreactive T cells.
  • Engineered donor-derived alloreactive T cells with a CD19 CAR construct for evaluation.
  • Integrated single-cell TCR and RNA sequencing for functional profiling of CAR T cell clones.
  • No new acute GvHD cases were observed post-CAR T cell infusion in patients with previous GvHD history.
  • CAR engagement alone led to contraction and functional exhaustion of alloreactive CAR T cells.
  • Inhibition of the PI3K/AKT/mTOR pathway improved CAR T cell persistence and effector function.

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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