Academic Journal
Real-world insights into genomic reprogramming during CAR-T cell manufacturing in India.
| Title: | Real-world insights into genomic reprogramming during CAR-T cell manufacturing in India. |
|---|---|
| Authors: | Das N; Department of Pathology, School of Medicine, Amrita Vishwa Vidyapeetham, Faridabad, Haryana, India., Mehta P; Department of Medical Oncology, School of Medicine, Amrita Vishwa Vidyapeetham, Faridabad, Haryana, India., Gupta K; Department of Pathology, School of Medicine, Amrita Vishwa Vidyapeetham, Faridabad, Haryana, India., Katharia R; Department of Transfusion Medicine, School of Medicine, Amrita Vishwa Vidyapeetham, Faridabad, Haryana, India., Pabbi S; Department of Transfusion Medicine, School of Medicine, Amrita Vishwa Vidyapeetham, Faridabad, Haryana, India., Mishra P; Department of Medical Oncology, School of Medicine, Amrita Vishwa Vidyapeetham, Faridabad, Haryana, India., Morya S; Department of Pathology, School of Medicine, Amrita Vishwa Vidyapeetham, Faridabad, Haryana, India. |
| Source: | Frontiers in immunology [Front Immunol] 2026 Sep 03; Vol. 17, pp. 1912690. Date of Electronic Publication: 2026 Sep 03 (Print Publication: 2026). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Lausanne : Frontiers Research Foundation] |
| MeSH Terms: | Immunotherapy, Adoptive*/methods , Receptors, Chimeric Antigen*/genetics , Receptors, Chimeric Antigen*/immunology , Cellular Reprogramming*/genetics , T-Lymphocytes*/immunology , T-Lymphocytes*/metabolism, Humans ; India ; Gene Expression Profiling ; Leukapheresis ; Genomics |
| 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® platform with a targeted immune-oncology panel comprising 750 genes. 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. (Copyright © 2026 Das, Mehta, Gupta, Katharia, Pabbi, Mishra and Morya.) |
| Competing Interests: | The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
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| Contributed Indexing: | Keywords: CAR-T; NanoString; genomic profiling; immune cells; leukapheresis; reactome pathway |
| Substance Nomenclature: | 0 (Receptors, Chimeric Antigen) |
| Entry Date(s): | Date Created: 20260918 Date Completed: 20260918 Latest Revision: 20260919 |
| Update Code: | 20260919 |
| PubMed Central ID: | PMC13582263 |
| DOI: | 10.3389/fimmu.2026.1912690 |
| PMID: | 42756106 |
| Database: | MEDLINE |
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