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Review
. 2020 Aug 26:10:1594.
doi: 10.3389/fonc.2020.01594. eCollection 2020.

Chimeric Antigen Receptor T-Cells in B-Acute Lymphoblastic Leukemia: State of the Art and Future Directions

Uri Greenbaum  1 , Kris Michael Mahadeo  1 , Partow Kebriaei  1 , Elizabeth J Shpall  1 , Neeraj Y Saini  1
Affiliations
Review

Chimeric Antigen Receptor T-Cells in B-Acute Lymphoblastic Leukemia: State of the Art and Future Directions

Uri Greenbaum et al. Front Oncol. .

Abstract

Use of adoptive T-cell therapy modified with chimeric antigen receptor (CAR-T) has revolutionized treatment of patients with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL). CAR-T cells directed against CD19 antigen have produced response rates as high as 90% in clinical trials for r/r B-ALL. Despite high rates of complete remissions, the durability of responses has been sub-optimal with frequent relapses, especially in adult B-ALL population. Systemic toxicities from CAR-T therapy and standardization of toxicities grading and management is another major hurdle in the development of CAR-T field. In this review, we discuss the latest evidence of CAR-T therapy in B-ALL, potential mechanisms of relapse and barriers to CAR-T cell therapy in B-ALL. We also debate the role of allogeneic hematopoietic stem cell transplant (allo-HCT) post CAR-T therapy.

Keywords: B-ALL; CAR-T therapy; acute lymphoblastic leukemia; allogeneic transplant after CAR-T therapy; chimeric antigen receptor; relapse after CAR-T therapy.

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References

    1. Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. . Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. (2014) 371:1507–17. 10.1056/NEJMoa1407222 - DOI - PMC - PubMed
    1. Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak O, et al. . Chimeric antigen receptor T cells in refractory B-cell lymphomas. N Engl J Med. (2017) 377:2545–54. 10.1056/NEJMoa1708566 - DOI - PMC - PubMed
    1. Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. . Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. (2018) 378:439–48. 10.1056/NEJMoa1709866 - DOI - PMC - PubMed
    1. Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, et al. . Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. (2019) 20:31–42. 10.1016/S1470-2045(18)30864-7 - DOI - PMC - PubMed
    1. Eshhar Z, Waks T, Gross G, Schindler DG. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci USA. (1993) 90:720–4. 10.1073/pnas.90.2.720 - DOI - PMC - PubMed

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