Utilization of donor CLL-1 CAR-T cells for the treatment of relapsed of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation
BackgroundHuman 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 cel...
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Frontiers Media S.A.
2025-01-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1491341/full |
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| author | Meng Zhang Meng Zhang Xiaomei Zhang Xiaomei Zhang Jiaxi Wang Wenyi Lu Xia Xiao Hairong Lyu Xiaoyuan He Yedi Pu Juanxia Meng Cuicui Lyu Xinping Cao Mingfeng Zhao Mingfeng Zhao |
| author_facet | Meng Zhang Meng Zhang Xiaomei Zhang Xiaomei Zhang Jiaxi Wang Wenyi Lu Xia Xiao Hairong Lyu Xiaoyuan He Yedi Pu Juanxia Meng Cuicui Lyu Xinping Cao Mingfeng Zhao Mingfeng Zhao |
| author_sort | Meng Zhang |
| collection | DOAJ |
| description | BackgroundHuman 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.Methods14 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:0.5×106/kg, Group B:1×106/kg, Group C:1.5×106/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.ResultsCLL-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 (P < 0.01).ConclusionsThe 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 registrationhttps://www.chictr.org.cn/, identifier ChiCTR2000041054. |
| format | Article |
| id | doaj-art-42215376590841d6a0a6a579fed512b8 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-42215376590841d6a0a6a579fed512b82025-01-17T06:50:39ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14913411491341Utilization of donor CLL-1 CAR-T cells for the treatment of relapsed of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantationMeng Zhang0Meng Zhang1Xiaomei Zhang2Xiaomei Zhang3Jiaxi Wang4Wenyi Lu5Xia Xiao6Hairong Lyu7Xiaoyuan He8Yedi Pu9Juanxia Meng10Cuicui Lyu11Xinping Cao12Mingfeng Zhao13Mingfeng Zhao14Hematology Center, National Key Clinical Discipline of Pediatric Hematology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, ChinaDepartment of Hematology, Tianjin First Central Hospital, Tianjin, ChinaDepartment of Hematology, Tianjin First Central Hospital, Tianjin, ChinaSchool of Medicine, Nankai University, Tianjin, ChinaDepartment of Hematology, Tianjin First Central Hospital, Tianjin, ChinaDepartment of Hematology, Tianjin First Central Hospital, Tianjin, ChinaDepartment of Hematology, Tianjin First Central Hospital, Tianjin, ChinaDepartment of Hematology, Tianjin First Central Hospital, Tianjin, ChinaDepartment of Hematology, Tianjin First Central Hospital, Tianjin, ChinaDepartment of Hematology, Tianjin First Central Hospital, Tianjin, ChinaDepartment of Hematology, Tianjin First Central Hospital, Tianjin, ChinaDepartment of Hematology, Tianjin First Central Hospital, Tianjin, ChinaDepartment of Hematology, Tianjin First Central Hospital, Tianjin, ChinaDepartment of Hematology, Tianjin First Central Hospital, Tianjin, ChinaSchool of Medicine, Nankai University, Tianjin, ChinaBackgroundHuman 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.Methods14 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:0.5×106/kg, Group B:1×106/kg, Group C:1.5×106/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.ResultsCLL-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 (P < 0.01).ConclusionsThe 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 registrationhttps://www.chictr.org.cn/, identifier ChiCTR2000041054.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1491341/fullCLL-1CAR-TAMLDonor-derivedHSCT |
| spellingShingle | Meng Zhang Meng Zhang Xiaomei Zhang Xiaomei Zhang Jiaxi Wang Wenyi Lu Xia Xiao Hairong Lyu Xiaoyuan He Yedi Pu Juanxia Meng Cuicui Lyu Xinping Cao Mingfeng Zhao Mingfeng Zhao Utilization of donor CLL-1 CAR-T cells for the treatment of relapsed of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation Frontiers in Immunology CLL-1 CAR-T AML Donor-derived HSCT |
| title | Utilization of donor CLL-1 CAR-T cells for the treatment of relapsed of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation |
| title_full | Utilization of donor CLL-1 CAR-T cells for the treatment of relapsed of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation |
| title_fullStr | Utilization of donor CLL-1 CAR-T cells for the treatment of relapsed of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation |
| title_full_unstemmed | Utilization of donor CLL-1 CAR-T cells for the treatment of relapsed of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation |
| title_short | Utilization of donor CLL-1 CAR-T cells for the treatment of relapsed of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation |
| title_sort | utilization of donor cll 1 car t cells for the treatment of relapsed of acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation |
| topic | CLL-1 CAR-T AML Donor-derived HSCT |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1491341/full |
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