European Hematology Association: First-in-Human CLL1-CD33 Compound CAR T Cells as a Two-Pronged Approach for the Treatment of Refractory Acute Myeloid Leukemia

Purpose: To firstly study the anti-leukemic activity of the CLL1-CD33 compound CAR in vitro and in vivo and consequently offer opportunities to the treatment for refractory and relapsed AML patients.

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Methods: We generated a cCAR targeting both CLL1 and CD33, then we evaluated the anti-leukemic activity by killing assays with multiple cell lines and in mouse models, next we study the depletion of CAR T cells in mouse body, finally we completed the first case of phase I clinical trial in a refractory AML patient.

Results: We successfully generated a cCAR that contains two independent complete units targeting CD33 that for a bulky leukemia and CLL1 for leukemic stem cells. In vitro assays indicated that CLL1-CD33 cCAR had specific anti-tumor activity against cell lines engineered expressing CLL1 or CD33, as well as leukemia samples from AML patients. In mouse models generated by cell lines engineered expressing CLL1 or CD33 and AML cell line U937 cells, the cCAR T cells significantly reduced tumor burden and prolonged survival. CD52 specific antibody CAMPATH could be used as a safety-switch to rapidly terminate cCAR therapy in mouse models. In the first-in-human phase 1 clinical trial, CLL1-CD33 cCAR T therapy was safe and well tolerated, and achieved complete response (CR).

Conclusion: Our preclinical study has shown that our CLL-1-CD33 cCAR possesses consistent, specific, and potent anti-tumor activity against CLL-1+ and/or CD33+ leukemia cells in vitro and in vivo. cCAR may have advantages over single-CAR therapy in terms of reduction of disease relapse by targeting LSC and bulky AML population. Phase 1 trial for CLL-1-CD33 cCAR are underway.

Presenter: Dr Fang Liu
Affiliation: Department of Hematology, Chengdu Military General Hospital, Chengdu, Sichuan, P.R. China

Abstract S149 will be presented by Fang Liu on Friday, June 15, 15:45-16:00 in Room A1.

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STOCKHOLM, June 15, 2018 /PRNewswire/ —

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