• CAR T-Cell Therapy for Non-B-cell acute leukemia
  • Mahdi Bagheri,1,*
    1. Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran


  • Introduction: CAR T-Cell Therapy for Non-B-cell acute leukemia Introduction: T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML) are both included in the category of non-B-cell acute leukemia. AML is a type of hematological cancer that develops from the aberrant clonal expansion of primary myeloid cells. The malignant transformation of immature T-cell progenitors causes T-ALL, a very invasive type of hematological cancer. The therapeutic efficacy of available therapies for refractory or relapsed (R/R) non-B-cell acute leukemia is currently constrained. Given its encouraging outcomes in the treatment of B-cell acute lymphoblastic leukemia (B-ALL), chimeric antigen receptor (CAR)-T cell therapy may be a potential strategy to treat non-B-cell acute leukemia in such circumstances. We list the characteristics of non-B-cell acute leukemia and the effectiveness of CAR-T for treating it in this review. Benefits of CAR-T therapy When compared to TCRs, CARs are independent of the major histocompatibility complex (MHC) and can detect specific antigens presence on the surface of cells. Because they are MHC independent, CAR-T cells are better suited for the treatment of tumors. By identifying tumor-specific antigens (TSA) on the surface of tumor cells, CAR-T cells destroy cancerous cells while causing the least amount of damage to healthy tissues. CAR-T therapy challenges for non-B-cell acute leukemia Fratricide, malignant contamination, T-cell aplasia for T-ALL, antigen heterogeneity, and immunosuppressive environments are only a few of the particular difficulties facing the development of CAR-T treatment for non-B-cell acute leukemia. CAR-T therapy's antigen targets for treating T-ALL About 80%–95% of T-ALL or T lymphoblastic lymphoma (TLL) display CD5, a surface marker of T-cell malignancies. Normal expression of CD5 on mature peripheral blood T cells, thymocytes, and certain B-cell lymphocytes in healthy tissues promotes CAR-T cell fratricide. For CD5+ hematological malignancies, CD5 is a hopeful target. All mature T-cells largely display the pan-T-cell surface antigen CD3, but due to the total fratricide of CAR-T cells, the development of CAR-T targeting CD3 is restricted in the early stages. Clinical use of CARs targeting CD3 is constrained due to the fact that T-ALL and TLL cells produced from patients often display cytoplasmic CD3 (cCD3) rather than membrane CD3 (mCD3). Over 95% of ALL, 30% of AML, and some lymphomas express CD7, a member of the Ig superfamily. Initially, CAR-T cells directed against CD7 displayed total fratricide and could not be used; however, in recent clinical trials, CD7 CAR have demonstrated satisfactory efficacy and safety. Fratricide can now be eliminated using gene editing technologies such as CRISPR-Cas9, TALEN, or PEBL. Most TLLs and certain T-ALLs express CD4, and this expression is only found in the hematopoietic compartment. As the CAR's target, it may lessen the adverse effects on tissues other than hematological ones. However, the survival of CD4 CAR T cells after the excision of tumor cells can result in the aplasia of CD4 positive T cells and an illness similar to HIV/AIDS. CAR-T therapy's antigen targets in AML CD123, which is expressed at low levels in early hematopoietic cells such hematopoietic stem/progenitor cells (HSPCs), is one potential target for AML. Because of CD123 ability that can discriminate HSC from leukemia stem cells(LSCs), to eradicate LSCs and maintain normal HSC, TALEN gene-editing technology was employed to create a TCRαβ negative allogeneic CD123 CAR (UCART123), which eradicate primary AML. The anti-tumor efficacy, proliferation, and perseverance of CD33 CAR-T cells may be impacted by various costimulators, distinct generation CAR constructions, and PI3K inhibitors. CD33 CAR demonstrated effective anti-AML activity in vitro. More than 80% of LSCs and AML blasts express C-type lectin-like molecule-1 (CLL-1). In pre-clinical studies, CLL1 CAR shown encouraging anti-tumor effectiveness, and in AML patients, it demonstrated anti-AML efficacy. Most AML blasts and AML stem/progenitor cells express CD70, a tumor necrosis factor (TNF) receptor ligand. In the clinical trial, more research on the CD70 CAR's efficacy and safety in patients is required.
  • Methods: this is a review article and doesn't have this part
  • Results: this is a review article and doesn't have this part
  • Conclusion: Conclusion T-ALL and AML are types of leukemia that have more complicated morphological characteristics than B-ALL and are linked to a poor prognosis. T-ALL and AML also have fewer therapy choices available after recurrence or refractory. Given the enormous success of CAR-T cell therapy in B-cell malignancies, adopting a similar strategy for non-B-cell acute leukemia seems to be a potential path for the creation of better therapies.
  • Keywords: T-ALL, AML, CAR T-Cell Therapy, leukemia