ArticleFrontiers in immunology2026
Real-world insights into genomic reprogramming during CAR-T cell manufacturing in India.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: While CAR-T cell therapy has transformed outcomes in B-cell malignancies, most genomic insights originate from clinical trials. There is a paucity of data describing molecular changes during CAR-T manufacturing in real-world practice, particularly for non-US CAR constructs. Methods: This was an observational study conducted at a tertiary care center in India where a total of 4 set of paired samples comprising leukapheresis starting material (n=4) and the corresponding final CAR-T cell product (n=4) were analyzed. Analysis was done using NanoString nCounter Results: Comparative gene expression analysis between CAR-T product and leukapheresis sample revealed significant upregulation of genes associated with cell proliferation (MKI67, BUB1), cytokine responsiveness (IL2RA, IL12RB2, CISH), metabolic fitness (PHGDH, PSAT1), and effector differentiation (IRF4, BATF3, LIF) in final product as compared to leukapheresis sample. Concurrent downregulation of innate immune and myeloid lineage genes (CD14, FCGR3A/B, FCAR, CYBB, FPR1, LILRA5, TYROBP, S100A12) along with reduced expression of inflammatory mediators (FOS, DUSP1, S100A12) suggests a controlled activation state that may limit baseline inflammatory priming and effective enrichment of adaptive T cells. Conclusions: Indigenous CAR-T manufacturing processes induce significant transcriptomic remodeling and reflects a highly proliferative and cytokine-responsive CAR-T phenotype associated with improved functional fitness. These findings may reflect a baseline framework for CAR-T genomic characterization in real-world clinical settings to explore outcome-related analyses.
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