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Strategies for having a more effective and less toxic CAR T-cell therapy for acute lymphoblastic leukemia.

ABSTRACT: In the recent years, using genetically modified T cells has been known as a rapid developing therapeutic approach due to the heartwarming results of clinical trials with patients suffering from relapsed or refractory (R/R) hematologic malignancies such as R/R Acute Lymphoblastic Leukemia (R/R ALL). One of these renowned approaches is Chimeric antigen receptors (CARs). CARs are synthetic receptors with the ability to be expressed on the surface of T lymphocytes and are specifically designed to target a tumor-associated antigen (TAA) of interest. CAR-expressing T cells have the capability of proliferating and maintaining their immunological functionality in the recipient body but like any other therapeutic approach, the safety, effectiveness, and specificity enhancement of CAR T cells still lingers in the ambiguity arena. Genetic manipulation methods, expansion protocols, infusion dosage, and conditioning regimens are all among crucial factors which can affect the efficacy of CAR T cell-based cancer therapy. In this article, we discuss the studies that have focused on various aspects that affect the efficacy and persistence of CAR T-cell therapy for ALL treatment and provide a widespread overview regarding the practical approaches capable of elevating the effectiveness and lessening the relative toxicities attributed to it.

SUBMITTER: Hashem Boroojerdi M

PROVIDER: S-EPMC7549730 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Strategies for having a more effective and less toxic CAR T-cell therapy for acute lymphoblastic leukemia.

Hashem Boroojerdi Mohadese M Rahbarizadeh Fatemeh F Safarzadeh Kozani Pouya P Kamali Elahe E Safarzadeh Kozani Pooria P

Medical oncology (Northwood, London, England) 20201012 11

In the recent years, using genetically modified T cells has been known as a rapid developing therapeutic approach due to the heartwarming results of clinical trials with patients suffering from relapsed or refractory (R/R) hematologic malignancies such as R/R Acute Lymphoblastic Leukemia (R/R ALL). One of these renowned approaches is Chimeric antigen receptors (CARs). CARs are synthetic receptors with the ability to be expressed on the surface of T lymphocytes and are specifically designed to ta ...[more]

PMID: 33047234

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Project description:BackgroundCD19-specific chimeric antigen receptor (CAR) T cells induce high rates of initial response among patients with relapsed B-cell acute lymphoblastic leukemia (ALL) and long-term remissions in a subgroup of patients.MethodsWe conducted a phase 1 trial involving adults with relapsed B-cell ALL who received an infusion of autologous T cells expressing the 19-28z CAR at the Memorial Sloan Kettering Cancer Center (MSKCC). Safety and long-term outcomes were assessed, as were their associations with demographic, clinical, and disease characteristics.ResultsA total of 53 adults received 19-28z CAR T cells that were manufactured at MSKCC. After infusion, severe cytokine release syndrome occurred in 14 of 53 patients (26%; 95% confidence interval [CI], 15 to 40); 1 patient died. Complete remission was observed in 83% of the patients. At a median follow-up of 29 months (range, 1 to 65), the median event-free survival was 6.1 months (95% CI, 5.0 to 11.5), and the median overall survival was 12.9 months (95% CI, 8.7 to 23.4). Patients with a low disease burden (<5% bone marrow blasts) before treatment had markedly enhanced remission duration and survival, with a median event-free survival of 10.6 months (95% CI, 5.9 to not reached) and a median overall survival of 20.1 months (95% CI, 8.7 to not reached). Patients with a higher burden of disease (≥5% bone marrow blasts or extramedullary disease) had a greater incidence of the cytokine release syndrome and neurotoxic events and shorter long-term survival than did patients with a low disease burden.ConclusionsIn the entire cohort, the median overall survival was 12.9 months. Among patients with a low disease burden, the median overall survival was 20.1 months and was accompanied by a markedly lower incidence of the cytokine release syndrome and neurotoxic events after 19-28z CAR T-cell infusion than was observed among patients with a higher disease burden. (Funded by the Commonwealth Foundation for Cancer Research and others; ClinicalTrials.gov number, NCT01044069 .).

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Strategies for having a more effective and less toxic CAR T-cell therapy for acute lymphoblastic leukemia.

Publications

Strategies for having a more effective and less toxic CAR T-cell therapy for acute lymphoblastic leukemia.

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