![]() ![]() Expression of FLT3 receptor and response to FLT3 ligand by leukemic cells. Structure-Function Analysis of FLT3 Ligand-FLT3 Receptor Interactions Using a Rapid Functional Screen. Far-red fluorescent tags for protein imaging in living tissues. A brief review concerning Chimeric Antigen Receptors T cell therapy. FMS-like Tyrosine Kinase 3/FLT3: From Basic Science to Clinical Implications. Preclinical Development of Anti-FLT3 CAR-T Therapy for the Treatment of Acute Myeloid Leukemia. Allogeneic FLT3 CAR T Cells with an Off-Switch Exhibit Potent Activity against AML and Can Be Depleted to Expedite Bone Marrow Recovery. Available online: (accessed on 30 September 2021). ![]() Amgen A Phase 1 Study Evaluating the Safety, Tolerability, and Efficacy of FLT3 Chimeric Antigen Receptor T-Cell (CAR-T) AMG 553 in Subjects With FLT3-Positive Relapsed/Refractory Acute Myeloid Leukemia.CAR T-cells targeting FLT3 have potent activity against FLT3−ITD+ AML and act synergistically with the FLT3-inhibitor crenolanib. Targeting FLT3 in acute myeloid leukemia using ligand-based chimeric antigen receptor-engineered T cells. Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor–modified T cells. CD33-specific chimeric antigen receptor T cells exhibit potent preclinical activity against human acute myeloid leukemia. CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid leukemia and multiple myeloma. State-of-Art of Cellular Therapy for Acute Leukemia. Effects of dendritic cell-activated and cytokine-induced killer cell therapy on 22 children with acute myeloid leukemia after chemotherapy. Immunotherapy of high-risk acute leukemia with a recipient (autologous) vaccine expressing transgenic human CD40L and IL-2 after chemotherapy and allogeneic stem cell transplantation. Dendritic Cell-Based and Other Vaccination Strategies for Pediatric Cancer. Outcome of αβ T cell-depleted transplantation in children with high-risk acute myeloid leukemia, grafted in remission. ![]() The authors have no conflict of interest to declare. Based on this result, we conclude that Flt3-CAR recognizes its target directly through the Flt3Lg binding site. Moreover, we show that an excess of soluble Flt3Lg effectively inhibits the interaction of Flt3-CAR with Flt3. We demonstrate that Flt3-CAR with the full-length soluble Flt3Lg polypeptide does not affect the proliferation of the Flt3-negative U937 cells, even at E:T = 5:1, indicating negligible off-target activity and higher specificity of activation compared with the use of an isolated binding domain. The full-length sequence of soluble human Flt3Lg cytokine used by us in this study is about 50 amino acids longer than the fragment used by Wang et al. The developed FLT3L CAR T cells showed specific activity towards Flt3-positive THP-1, MV4-11, and MOLM13 cell lines, albeit that they also showed a weak cytotoxic effect towards the Flt3-negative cell line U937 as soon as effector : target ratio (E:T) = 1:1. , who used the isolated receptor-binding domain of Flt3Lg as a recognition module in chimeric receptors. The robust in vitro antitumor effects of Flt3-CAR T cells, combined with their low off-target cytotoxicity, hold promise for AML treatment.Ī similar approach was reported by Wang et al. The developed system can be viewed as a non-immunogenic functional equivalent of scFv-mediated targeting. Finally, we confirm the authenticity of targeting by its competitive dose-dependent inhibition with a soluble Flt3-ligand. We prove that the inherent cytolytic capacity of T cells is essential for the killing. We demonstrate specific killing of Flt3-positive THP-1 cells by Flt3-CAR T cells and the lack of cytotoxicity towards Flt3-negative U937 cells. ![]() Here, we design a chimeric receptor with a full-length natural Flt3-ligand recognition module that targets Flt3 tyrosine kinase, known as an adverse marker in AML. The recognition involves the extracellular portion of the CAR protein, which corresponds to either the antibody or the physiological binding partner of the targeted antigen. CARs promote immune reactions through recognition of the target molecular epitopes at the surface of cancer cells. Chimeric antigen receptor (CAR) approaches for AML are being actively developed. Relapsed/refractory acute myeloid leukemia (AML) cannot be cured with chemotherapy alone, as the blasts survive the treatment. ![]()
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