Treatment of Aggressive T Cell Lymphoblastic Lymphoma/leukemia Using Anti-CD5 CAR T Cells
| Autor: | Masayuki Wada, Lei Xu, Li-hua Sun, Hongyu Zhang, William M Hanes, Jia Feng, Huiming Shan, Qian Zhang, Kevin G. Pinz, Zehua Wu, Xingen Wang, Yupo Ma, Wenli Zhang, Andrew Cinquina, Xun Jiang, Ping Zhang, Qi Chen, Haichan Xu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment T cell T-Lymphocytes Immunotherapy Adoptive Article T cell lymphoma 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases medicine T-cell lymphoma Humans Interleukin-15 Hematopoietic cells business.industry Lymphoblastic lymphoma Immunotherapy CD5 CAR and IL15/IL15sushi Precursor Cell Lymphoblastic Leukemia-Lymphoma medicine.disease Lymphoma Leukemia 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Stem cell CD5 business |
| Zdroj: | Stem Cell Reviews and Reports |
| ISSN: | 2629-3277 |
| Popis: | While treatment for B-cell malignancies has been revolutionized through the advent of CAR immunotherapy, similar strategies for T-cell malignancies have been limited. Additionally, T-cell leukemias and lymphomas can commonly metastasize to the CNS, where outcomes are poor and treatment options are associated with severe side effects. Consequently, the development of safer and more effective alternatives for targeting malignant T cells that have invaded the CNS remains clinically important. CD5 CAR has previously been shown to effectively target various T-cell cancers in preclinical studies. As IL-15 strengthens the anti-tumor response, we have modified CD5 CAR to secrete an IL-15/IL-15sushi complex. In a Phase I clinical trial, these CD5-IL15/IL15sushi CAR T cells were tested for safety and efficacy in a patient with refractory T-LBL with CNS infiltration. CD5-IL15/IL15sushi CAR T cells were able to rapidly ablate the CNS lymphoblasts within a few weeks, resulting in the remission of the patient’s lymphoma. Despite the presence of CD5 on normal T cells, the patient only experienced a brief, transient T-cell aplasia. These results suggest that CD5-IL15/IL15sushi CAR T cells may be a safe and useful treatment of T-cell malignancies and may be particularly beneficial for patients with CNS involvement.Graphical Abstract |
| Databáze: | OpenAIRE |
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