Treatment of Aggressive T Cell Lymphoblastic Lymphoma/leukemia Using Anti-CD5 CAR T Cells

Stem Cell Reviews and Reports - 2021
Jia Feng1, Hai-chan Xu1, Andrew Cinquina2, Zehua Wu1, Qi Chen1, Ping Zhang1, Xingen Wang3, Huiming Shan4, Lei Xu1, Qian Zhang1, Lihua Sun1, Wenli Zhang1, Kevin G. Pinz2, M. Wada2, Xun Jiang2, William Hanes2, Yupo Ma2, Hongyu Zhang1
1Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China
2iCell Gene Therapeutics LLC Research & Development Division Long Island High Technology Incubator, Stony Brook, USA
3Department of Pathology, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China
4Department of Radiology, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China

Tóm tắt

AbstractWhile 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

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