Anti-CLL1 Chimeric Antigen Receptor T-Cell Therapy in Children with Relapsed/Refractory Acute Myeloid Leukemia
| Autor: | Yingyi He, Hui Zhang, Hua Jiang, Peng-Fei Wang, Zhuo-Yan Li, Wenting Gan |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty medicine.medical_treatment Cell- and Tissue-Based Therapy Immunotherapy Adoptive 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans Child Chemotherapy Receptors Chimeric Antigen business.industry Myeloid leukemia medicine.disease Minimal residual disease Chimeric antigen receptor Cytokine release syndrome Haematopoiesis Leukemia Myeloid Acute 030104 developmental biology 030220 oncology & carcinogenesis Leukocytes Mononuclear Chimeric Antigen Receptor T-Cell Therapy Stem cell business |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 27(13) |
| ISSN: | 1557-3265 |
| Popis: | Purpose: The survival rate of children with refractory/relapsed acute myeloid leukemia (R/R-AML) by salvage chemotherapy is minimal. Treatment with chimeric antigen receptor T cells (CAR T) has emerged as a novel therapy to improve malignancies treatment. C-type lectin-like molecule 1 (CLL1) is highly expressed on AML stem cells, blast cells, and monocytes, but not on normal hematopoietic stem cells, indicating the therapeutic potential of anti-CLL1 CAR T in AML treatment. This study aimed to test the safety and efficacy of CAR T-cell therapy in R/R-AML. Patients and Methods: Four pediatric patients with R/R-AML were enrolled in the ongoing phase I/II anti-CLL1 CAR T-cell therapy trial. The CAR design was based on an apoptosis-inducing gene, FKBP-caspase 9, to establish a safer CAR (4SCAR) application. Anti-CLL1 CAR was transduced into peripheral blood mononuclear cells of the patients via lentivector 4SCAR, followed by infusion into the recipients after lymphodepletion chemotherapy. Cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, and other adverse events were documented. Treatment response was evaluated by morphology and flow cytometry–based minimal residual disease assays. Results: Three patients with R/R-AML achieved complete remission and minimal residual disease negativity, while the other patient remained alive for 5 months. All these patients experienced low-grade and manageable adverse events. Conclusions: On the basis of our single-institution experience, autologous anti-CLL1 CAR T-cell therapy has the potential to be a safe and efficient alternative treatment for children with R/R-AML, and therefore requires further investigation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|