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December 8, 2025Blood

Identification of CD4+ T cells targeting DM-sensitive antigens presented on mismatched HLA-DP alleles, as mediators of a selective graft-versus-leukemia effect.

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Authors

KKKlaus KornKGKatharina GötzHBHeiko Bruns

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Overview

Findings show cytotoxicity and specific cytokine profiles in T cells targeting DM-sensitive antigens, suggesting a potential for leukemia-specific therapies without graft-versus-host disease.

Key Points

  • The study aims to identify CD4+ T cells that target DM-sensitive antigens on mismatched HLA-DP alleles to promote a selective graft-versus-leukemia effect.
  • Isolated CD4⁺ T cells were co-cultured with HeLa cells expressing various HLA-DP alleles.
  • T-cell clones were activated and expanded based on CD137 expression.
  • Characterization of T-cell reactivity used various cell lines and primary AML blasts.
  • TCR sequencing was performed for clones with favorable characteristics to generate TCR-engineered T cells.
  • CRISPR was employed for TCR reexpression in engineered T cells.
  • 79 of 105 T-cell clones targeted DM-sensitive antigens and showed limited recognition of non-hematopoietic cells.
  • DM-sensitive T-cell clones recognized HLA-DO positive malignant cells but not non-hematopoietic tissues.
  • Cytotoxicity was mediated by Granzyme A and B, with significant cytokine secretion including IL-6 and IL-13.
  • TCR-engineered T cells demonstrated high functionality post-reexpression, assessed via flow cytometry.

Cite This Study

Korn et al. (2025) studied this question.

synapsesocial.com/papers/69362f694fa91c937236df0ehttps://doi.org/10.1182/blood-2025-4235
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