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Editorial
. 2023 Nov 30;12(11):2970-2975.
doi: 10.21037/tcr-23-1396. Epub 2023 Nov 17.

A STEP ahead for CAR-T cell therapy of large B cell lymphoma: understanding the molecular determinants of resistance

Samir Mouhssine  1   2 , Nawar Maher  1   2 , Gianluca Gaidano  1   2
Affiliations
Editorial

A STEP ahead for CAR-T cell therapy of large B cell lymphoma: understanding the molecular determinants of resistance

Samir Mouhssine et al. Transl Cancer Res. .
No abstract available

Keywords: Large B cell lymphoma (LBCL); axicabtagene ciloleucel (axi-cel); chimeric antigen receptor (CAR)-T cells; simultaneous tumor and effector profiling; treatment resistance.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-1396/coif). G.G. declares advisory board and speaker’s bureau honoraria from AbbVie, AstraZeneca, BeiGene, Incyte, Janssen, and Roche. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
The STEP platform analysis. In the tumor microenvironment of a patient undergoing CAR19 T cell therapy, dead cells release cell free DNA, which can derive from tumor cells (ctDNA), CAR-T cells (cfCAR19), or non-engineered T cells (cfTCR). Serial blood samples were collected from patients and plasma was separated to measure ctDNA, cfCAR19, and cfTCR at different timepoints: (I) previously to lymphodepletion; (II) before CAR19 T cell infusion; (III) post-CAR19 T cell infusion, at week 1, 2, 3, 4, and after the fourth week from the administration; (IV) at relapse, if applicable. Collected data led to the development of the STEP score, which combines ctDNA and cfCAR19 at week 4 and at week 1, respectively, capable of predicting EFS and OS. Created with BioRender.com. CAR19 T cell, CAR-T cells directed against CD19; CAR, chimeric antigen receptor; ctDNA, circulating tumor DNA; cfCAR19, cell free CAR19 DNA; cfTCR, T cell receptor cfDNA; STEP, Simultaneous Tumor and Effector Profiling; EFS, event free survival; OS, overall survival.
See this image and copyright information in PMC

Comment on

  • Determinants of resistance to engineered T cell therapies targeting CD19 in large B cell lymphomas.
    Sworder BJ, Kurtz DM, Alig SK, Frank MJ, Shukla N, Garofalo A, Macaulay CW, Shahrokh Esfahani M, Olsen MN, Hamilton J, Hosoya H, Hamilton M, Spiegel JY, Baird JH, Sugio T, Carleton M, Craig AFM, Younes SF, Sahaf B, Sheybani ND, Schroers-Martin JG, Liu CL, Oak JS, Jin MC, Beygi S, Hüttmann A, Hanoun C, Dührsen U, Westin JR, Khodadoust MS, Natkunam Y, Majzner RG, Mackall CL, Diehn M, Miklos DB, Alizadeh AA. Sworder BJ, et al. Cancer Cell. 2023 Jan 9;41(1):210-225.e5. doi: 10.1016/j.ccell.2022.12.005. Epub 2022 Dec 29. Cancer Cell. 2023. PMID: 36584673 Free PMC article.

References

    1. Kurz KS, Ott M, Kalmbach S, et al. Large B-Cell Lymphomas in the 5th Edition of the WHO-Classification of Haematolymphoid Neoplasms-Updated Classification and New Concepts. Cancers (Basel) 2023;15:2285. - PMC - PubMed
    1. Perales MA, Anderson LD, Jr, Jain T, et al. Role of CD19 Chimeric Antigen Receptor T Cells in Second-Line Large B Cell Lymphoma: Lessons from Phase 3 Trials. An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. Transplant Cell Ther 2022;28:546-59. 10.1016/j.jtct.2022.06.019 - DOI - PMC - PubMed
    1. Sermer D, Brentjens R. CAR T-cell therapy: Full speed ahead. Hematol Oncol 2019;37 Suppl 1:95-100. 10.1002/hon.2591 - DOI - PubMed
    1. De Marco RC, Monzo HJ, Ojala PM. CAR T Cell Therapy: A Versatile Living Drug. Int J Mol Sci 2023;24:6300. 10.3390/ijms24076300 - DOI - PMC - PubMed
    1. Roberts ZJ, Better M, Bot A, et al. Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL. Leuk Lymphoma 2018;59:1785-96. 10.1080/10428194.2017.1387905 - DOI - PubMed