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Chimeric antigen receptor T-cell therapy for T-ALL and AML.

ABSTRACT: Non-B-cell acute leukemia is a term that encompasses T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML). Currently, the therapeutic effectiveness of existing treatments for refractory or relapsed (R/R) non-B-cell acute leukemia is limited. In such situations, chimeric antigen receptor (CAR)-T cell therapy may be a promising approach to treat non-B-cell acute leukemia, given its promising results in B-cell acute lymphoblastic leukemia (B-ALL). Nevertheless, fratricide, malignant contamination, T cell aplasia for T-ALL, and specific antigen selection and complex microenvironment for AML remain significant challenges in the implementation of CAR-T therapy for T-ALL and AML patients in the clinic. Therefore, designs of CAR-T cells targeting CD5 and CD7 for T-ALL and CD123, CD33, and CLL1 for AML show promising efficacy and safety profiles in clinical trials. In this review, we summarize the characteristics of non-B-cell acute leukemia, the development of CARs, the CAR targets, and their efficacy for treating non-B-cell acute leukemia.

SUBMITTER: Wei W

PROVIDER: S-EPMC9745195 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Chimeric antigen receptor T-cell therapy for T-ALL and AML.

Wei Wenwen W Yang Dong D Chen Xi X Liang Dandan D Zou Liqun L Zhao Xudong X

Frontiers in oncology 20221129

Non-B-cell acute leukemia is a term that encompasses T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML). Currently, the therapeutic effectiveness of existing treatments for refractory or relapsed (R/R) non-B-cell acute leukemia is limited. In such situations, chimeric antigen receptor (CAR)-T cell therapy may be a promising approach to treat non-B-cell acute leukemia, given its promising results in B-cell acute lymphoblastic leukemia (B-ALL). Nevertheless, fratricide, m ...[more]

PMID: 36523990

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Project description:Outcomes for post-chimeric antigen receptor (CAR) T cell therapy (CART) relapse are poor. The utilization of a unique CAR T cell construct for post-CART failure is increasing, but this approach is not well described. In this study, with CART-A the first unique CAR T cell construct received and CART-B the second, the primary objective was to characterize outcomes following CART-B. Secondary objectives included evaluating safety and toxicity with sequential CART infusions; investigating the impact of potential factors, such as antigen modulation and interval therapy, on CART-B response; and characterizing long-term outcomes in patients receiving multiple CARTs. This was a retrospective review (NCT03827343) of children and young adults with B cell acute lymphoblastic leukemia (B-ALL) undergoing CART therapy who received at least 2 unique CART constructs, excluding interim CART reinfusions of the same product. Of 135 patients, 61 (45.1%) received 2 unique CART constructs, including 13 who received >2 CARTs over time. Patients included in this analysis received 14 distinct CARTs targeting CD19 and/or CD22. The median age at CART-A was 12.6 years (range, 3.3 to 30.4 years). The median time from CART-A to CART-B was 302 days (range, 53 to 1183 days). CART-B targeted a different antigen than CART-A in 48 patients (78.7%), owing primarily to loss of CART-A antigen target. The rate of complete remission (CR) was lower with CART-B (65.5%; 40 of 61) than with CART-A (88.5%; 54 of 61; P = .0043); 35 of 40 (87.5%) CART-B responders had CART-B targeting a different antigen than CART-A. Among the 21 patients with a partial response or nonresponse to CART-B, 8 (38.1%) received CART-B with the same antigen target as CART-A. Of 40 patients with CART-B complete response (CR), 29 (72.5%) relapsed. For the 21 patients with evaluable data, the relapse immunophenotype was antigennegative in 3 (14.3%), antigendim in 7 (33.3%), antigenpositive in 10 (47.6%), and lineage switch in 1 (4.8%). The median relapse-free survival following CART-B CR was 9.4 months (95% confidence interval [CI], 6.1 to 13.2 months), and overall survival was 15.0 months (95% CI, 13.0 to 22.7 months). Given the limited salvage options for post-CART relapse, identifying optimizing strategies for CART-B is critical. We raise awareness about the emerging use of CART for post-CART failure and highlight clinical implications accompanying this paradigm shift.

Dataset Information

Chimeric antigen receptor T-cell therapy for T-ALL and AML.

Publications

Chimeric antigen receptor T-cell therapy for T-ALL and AML.

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