151. CAR T cells targeting CD99 as an approach to eradicate T-cell acute lymphoblastic leukemia without normal blood cells toxicity
- Author
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Zhijie Zhang, Jiaxing Liu, Liang Huang, Anqi Ren, Xiqin Tong, You Qin, Yingqi Leng, Zhu Haichuan, Zhang Zijian, Tong-Cun Zhang, Zhe Li, Shangkun Zhang, Han Wu, Hong Cen, Xiyu Liu, Kunyu Yang, Jinjue Liang, Shi Jiangzhou, and Fuling Zhou
- Subjects
Cancer Research ,medicine.medical_specialty ,CAR T ,T cell ,Cell ,T-cell leukemia ,12E7 Antigen ,Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ,Immunotherapy, Adoptive ,Mice ,Antigen ,AML ,Cell Line, Tumor ,Internal medicine ,medicine ,Animals ,Humans ,Diseases of the blood and blood-forming organs ,Letter to the Editor ,Molecular Biology ,RC254-282 ,Blood Cells ,Receptors, Chimeric Antigen ,Hematology ,biology ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Leukemia ,medicine.anatomical_structure ,Oncology ,Cell culture ,Cancer research ,biology.protein ,Antibody ,CD99 ,RC633-647.5 ,business ,T-ALL ,Antitumor activity - Abstract
CAR T cell therapy has shown dramatic clinical success in relapsed or refractory (r/r) B-ALL and other haematological malignancies. However, the loss of specific antigens, cell fratricide, T cell aplasia, and normal T cell separation are challenges in treating T cell leukemia/lymphoma with CAR T therapy. CD99 is a promising antigen to target T-ALL and AML as it is expressed on the majority of T-ALL and AML. Here, we isolated a low-affinity CD99 (12E7) antibody, which specifically recognizes leukemia cells over normal bone marrow cells. T cells transduced with an anti-CD99-specific CAR that contained the 12E7 scFv expanded with minor fratricide, maintained their cytotoxic function and mediated powerful antitumour effects. Subsequently, we conducted a pilot clinical study to evaluate the safety and feasibility of therapy with anti-CD99 CAR T cells in 4 patients with r/r T-LBL (n=1), AML (n=2) or myeloid sarcoma (MS) (n=1). The clinical overall response rate (ORR) was 50% (2/4 patients), and 1 patients (25%) achieved complete remission (CR) for 2 month. Mild cytokine release syndrome (CRS) occurred in 2 patients and the CRS no more than grade 2. Together, our results demonstrate that anti-CD99 CAR T cells specifically recognize and efficiently eliminate CD99+ leukemia cells.
- Published
- 2021