To evaluate the safety and efficacy of anti Tim3/CD123 CAR-T cells in the treatment of relapsed and refractory acute myeloid leukemia.
Cluster of Differentiation 123 (CD123) is usually overexpressed on leukemia stem cells (LSCs) in acute myeloid leukemia (AML). However, CD123 has poor specificity and is also expressed on normal hematopoietic stem cells (HSC), myeloid cells, and some non-hematopoietic cells. This leads to widespread on-target off-tumor effect in the clinical application of anti CD123 CAR-T cells, manifested as severe bone marrow suppression, organ damage, and patients experiencing infections, bleeding, and organ dysfunction. T cell immunoglobulin and mucin domain 3 (Tim-3) belongs to the Tim gene family. 85% of LSCs highly express Tim-3, while normal hematopoietic stem/progenitor cells (HSC/P), granulocytes, and macrophages do not express Tim-3. Compared with CD123, seeing Tim-3 as a recognition tool for LSCs has higher specificity. In vivo and in vitro studies have confirmed that anti Tim-3 CAR-T cells have significant anti LSCs effects, while not affecting the ability of normal HSC/P to form colonies and differentiate lineages. We believe that using both Tim-3 and CD123 as targets for CAR-T cells can improve the specificity of recognizing LSCs, reduce the killing effect of CAR-T cells on HSC/P expressing CD123, and thus reduce the on-target off-tumor effect.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Enrolled patients will receive prespecified dose of autologous CAR-T cells.
Kailin Xu
Xuzhou, Jiangsu, China
RECRUITINGDose-limiting toxicity #DLT#
Adverse events assessed according to NCI-CTCAE v5.0
Time frame: Baseline up to 28 days after CAR-T cells infusion
MRD negative overall response rate (MRD- ORR)
Assessment of MRD negative overall response rate (MRD- ORR) at 3 months of treatment
Time frame: 3 months
Overall response rate (ORR)
Assessment of ORR (ORR = CR + CRi ) at Month 6, 12, 18 and 24
Time frame: Month 6, 12, 18 and 24
Event-free survival (EFS)
Assessment of EFS at Month 6, 12, 18 and 24
Time frame: Month 6, 12, 18 and 24
Overall survival (OS)
Assessment of OS at Month 6, 12, 18 and 24
Time frame: Month 6, 12, 18 and 24
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