Utilization of Donor CLL-1 CAR-T Cells for the Treatment of Relapsed of Acute Myeloid Leukemia Following Allogeneic Hematopoietic Stem Cell Transplantation

Overview

Journal Front Immunol

Date 2025 Feb 3

PMID 39896798

Authors

Meng Zhang

Xiaomei Zhang

Jiaxi Wang

Wenyi Lu

Xia Xiao

Hairong Lyu

Xiaoyuan He

Yedi Pu

Juanxia Meng

Cuicui Lyu

Xinping Cao

Mingfeng Zhao

Affiliations

Soon will be listed here.

Abstract

Background: Human C-type lectin-like molecule 1 (CLL-1) represents a promising therapeutic target for Chimeric antigen receptor T (CAR-T) cells therapy in the treatment of acute myeloid leukemia (AML). In this study, we aimed to evaluate the efficacy and safety profile of donor-derived CLL-1 CAR-T cells in AML patients who experienced relapsed post-transplantation.

Methods: 14 AML patients who experienced relapse following allogeneic HSCT were enrolled in our clinical trial. However, 2 patients withdrew from the study due to rapid disease progression. 12 participants received donor-derived CLL-1 CAR-T cells and were categorized into 3 groups based on the dosage of infused CAR-T cells dose (Group A:0.5×10/kg, Group B:1×10/kg, Group C:1.5×10/kg). And scRNA-seq was used to reveal CLL-1 CAR-T cells dynamics in a CAR-T cells infusion products and PBMCs at the peak of expansion for patient 4.

Results: CLL-1 CAR-T cells were well tolerated by all 12 patients. Cytokine Release Syndrome (CRS) was observed in all patients, with 5 patients experiencing grade ≥3. 3 patients developed cytokine release syndrome-associated encephalopathy (CRES), and 1 patient had a grade 4 severity level. All patients demonstrated a reduction in tumor burden, while 7 patients (58.33%) achieved MRD-CR and 2 patients (16.67%) reached MRD+CR. CAR-T cells expansion was detectable in all 12 patients, with the median time of peak expansion was 9 days (range: 7-11 days). In patient 4, compared to the pre-reinfusion state, CD4+ cells at the peak of expansion showed upregulation of cell killing-related genes and memory T cell-related genes ( < 0.01).

Conclusions: The CLL-1 CAR-T cells therapy derived from allogeneic donors demonstrates both safety and efficacy in the management of relapsed AML following allogeneic HSCT. And adjusting the ratio of CD4+ CAR-T cells and CD8+ CAR-T cells prior to infusion may help mitigate CAR-T cell-related side effects.

Clinical Trial Registration: https://www.chictr.org.cn/, identifier ChiCTR2000041054.

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