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December 8, 2025BloodOpen Access

CAR-T efficacy in large B-cell lymphoma is shaped by neoantigen-driven epitope spreading and limited by HLA loss and genomic instability

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Authors

CSConstanza Savid-FronteraMMMeghan MengesMCMonika Chojnacka

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Overview

Analysis reveals CAR-T enhances T cell responses in large B-cell lymphoma, suggesting neoantigen importance and impact of genomic instability.

Key Points

  • This research investigates factors affecting CAR-T therapy efficacy in large B-cell lymphoma (LBCL).
  • Analyzed genomes of 61 LBCL samples using bioinformatics and whole genome sequencing.
  • Compared neoantigen presence in patients responding to CAR-T versus those who progressed from treatment.
  • Utilized immunocompetent mouse models to study tumor responses post-CAR-T infusion.
  • Higher neoantigen burden was linked to better responses in CAR-T treated patients.
  • Genomic instability correlated with lower neoantigen recognition and poor outcomes.
  • eCD8 T cells were crucial for tumor clearance after CAR-T, particularly against non-CD19 targets.

Cite This Study

Savid-Frontera et al. (2025) studied this question.

synapsesocial.com/papers/693624d44fa91c937236d02ehttps://doi.org/10.1182/blood-2025-107
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