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Editorial
. 2023 Feb 16;29(4):694-696.
doi: 10.1158/1078-0432.CCR-22-3232.

Enhancing CD19 Chimeric Antigen Receptor T Cells Through Memory-Enriched T Cells

Ettaib El Marabti  1 , Omar Abdel-Wahab  1   2
Affiliations
Editorial

Enhancing CD19 Chimeric Antigen Receptor T Cells Through Memory-Enriched T Cells

Ettaib El Marabti et al. Clin Cancer Res. .

Abstract

Chimeric antigen receptor T (CAR-T) cells directed against CD19 have transformed the therapy of relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). A recent study reports promising activity and safety of CD19 CAR-T cells generated from naïve, stem, and central memory T cells in adults with R/R B-ALL. See related article by Aldoss et al., p. 742.

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Conflict of interest statement

CONFLICTS OF INTEREST:

O.A.-W. has served as a consultant for H3B Biomedicine, Foundation Medicine Inc., Merck, Prelude Therapeutics, and Janssen, and is on the Scientific Advisory Board of Envisagenics Inc., AIChemy, Harmonic Discovery Inc., and Pfizer Boulder; O.A.-W. has received prior research funding from H3B Biomedicine, Nurix Therapeutics, Minovia Therapeutics, and LOXO Oncology unrelated to the current manuscript. The remaining authors declare no competing interests. The remaining authors have nothing to disclose.

Figures

Figure.
Figure.. Generation of a novel CD19 CAR-T therapy via transduction of stem cell memory (Tcm), central memory, naïve (Tn/mem) T-cells.
Abxicabtagene ciloleucel and Tisagenlecleucel are U.S. FDA-approved anti-CD19 CAR-T cell therapies for relapsed/refractory B-ALL. Abxicabtagene ciloleucel is generated by transducing T cells with a gamma retroviral vector while Tisagenlecleucel is generated by transduction with a lentiviral vector containing the CD19 CAR transgene. Abxicabtagene ciloleucel and tisagenlecleucel have identical CD19 recognition (FMC63) and intracellular CD3-ζ signaling domains but defer in their costimulatory domains. Abxicabtagene ciloleucel possesses a CD28 costimulatory domain while CTL019 uses CD8-α and 4–1BB. In this issue, Aldoss and colleagues (1) present a novel CAR-T cells generated from stem cell memory (Tcm), central memory, and naïve (Tn/mem) T-cells. Peripheral blood mononuclear cells are obtained from leukapharesis. The leukapheresed material undergoes CD14+ monocyte and CD25+ T-reg depletion, followed by CD45RA+ depletion and CD62L+ enrichment to select for Tcm cells. CD45RA+ depletion can be omitted to allow for the inclusion of Tn/mem in the final cell population. These cells are activated and lentivirally transduced to express a CD19 receptor, CD28 costimulatory domain, and CD3-ζ signaling domain. (Figure created with Biorender.com.)
See this image and copyright information in PMC

Comment in

References

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