Relapsed/refractory acute myeloid leukemia (R/R AML) currently lacks effective CAR-T therapeutic agents due to the absence of tumor-specific target antigens. Most AML-associated antigens are expressed on normal hematopoietic stem/progenitor cells (HSPCs) and healthy tissues, increasing the risk of on-target off-tumor toxicity and non-neoplastic toxicity. CD33 is present on leukemic cells in over 80% of AML patients. Compared with CLL-1, CD123 and other targets, CD33 exhibits higher expression across diverse AML subtypes, reducing the risk of treatment failure and relapse caused by antigen escape and thus serving as an ideal therapeutic target for AML. However, conventional CD33-targeted CAR-T cells demonstrate suboptimal efficacy in clinical trials, accompanied by significant toxicity and inadequate in vivo expansion. To further investigate the safety and efficacy of CAR-T therapy for AML, our center has initiated a clinical trial of functionally optimized CD33 CAR-T (FO33 CAR-T) cells for R/R AML. We constructed a lentiviral CAR vector containing the CD33-targeting scFv, 4-1BB, and CD3ζ, followed by insertion of adjuvant molecule X. FO33 CAR-T cells showed superior cytotoxicity against AML cell lines and enhanced biological activity compared with conventional CD33 CAR-T cells, and exerted safe and effective antitumor effects in preclinical models. This single-center, open-label, prospective clinical trial aims to evaluate the safety and efficacy of FO33 CAR-T cells in patients with R/R AML, as well as to characterize the pharmacokinetic and pharmacodynamic (PK/PD) profiles of this therapy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Functionally optimized CD33 CAR-T intravenous infusion
Evaluate the Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of Functionally optimized CD33 CAR-T cell therapy in relapsed/refractory B Cell Acute Myeloid Leukemia
the incidence and severity of immune therapy related toxic reactions (irAEs)
Time frame: up to one month after the CAR-T infusion
Evaluate the Complete Response rate of Functionally optimized CD33 CAR-T cell therapy in relapsed/refractory B Cell Acute Myeloid Leukemia
Complete Response rate on M1 and M3
Time frame: one month and three month after the CAR-T infusion
Cell pharmacokinetics Dynamic indicators
CAR-T/T% by flow cytometry
Time frame: Day7, Day10, Day14, Day28 after the CAR-T infusion
long-term efficacy
Overall Survival
Time frame: up to one year after the CAR-T infusion
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