![]() Receptor affinity and extracellular domain modifications affect tumor recognition by ROR1-specific chimeric antigen receptor T cells. Novel CD19/CD22 bicistronic chimeric antigen receptors outperform single or bivalent cars in eradicating CD19+CD22+, CD19- and CD22- Pre-B Leukemia. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. Intent to treat leukemia remission by CD19CAR T cells of defined formulation and dose in children and young adults. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. One-year overall and event-free survival were 63% and 46%, respectively. Persistence was demonstrated in 11 of 14 patients at last follow-up, with enhanced CAR T cell expansion compared with published data. In a clinical study (CARPALL, NCT02443831), 12/14 patients with relapsed/refractory pediatric B cell acute lymphoblastic leukemia treated with CAT CAR T cells achieved molecular remission. CAT CAR T cells showed increased proliferation and cytotoxicity in vitro and had enhanced proliferative and in vivo antitumor activity compared with FMC63 CAR T cells. ![]() We generated a novel CD19 CAR (CAT) with a lower affinity than FMC63, the high-affinity binder used in many clinical studies 1, 2, 3, 4. There is evidence of a ceiling above which increased immunoreceptor affinity may adversely affect T cell responses 9, 10, 11. ![]() However, little is known about the impact of CAR binding affinity. Some factors, including the choice of single-chain spacer 6 and extracellular 7 and costimulatory domains 8, have a profound effect on CAR T cell function and persistence. Moreover, 40–60% of patients relapse owing to poor CAR T cell persistence or emergence of CD19 − clones. Nature Medicine volume 25, pages 1408–1414 ( 2019) Cite this articleĬhimeric antigen receptor (CAR)-modified T cells targeting CD19 demonstrate unparalleled responses in relapsed/refractory acute lymphoblastic leukemia (ALL) 1, 2, 3, 4, 5, but toxicity, including cytokine-release syndrome (CRS) and neurotoxicity, limits broader application. Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR
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