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Investigate how neoantigen-driven epitope spreading and genomic instability affect CAR-T efficacy in large B-cell lymphoma.

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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Investigate how neoantigen-driven epitope spreading and genomic instability affect CAR-T efficacy in large B-cell lymphoma.
Analyzed whole genome sequencing samples from CAR-T treated patients
Employed bioinformatics to predict immunogenic neoantigens
Used mathematical modeling to assess CAR-T dynamics
Conducted IFNγ ELISPOT assays in tumor infiltrating lymphocytes
No significant difference in predicted neoantigens between progressors and responders
Progressors showed a significantly lower neoantigen burden post-adjustment
Higher pre-treatment neoantigens associated with better CAR-T response
Enhanced tumor-specific reactivity of T cells observed post-infusion in some patients

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Analysis finds challenges in CAR-T response in large B-cell lymphoma linked to neoantigens and genomic instability.

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

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