Author: Veliz, Kimberly ; Diorio, Caroline ; Tasian, Sarah K ; Glisovic-Aplenc, Tina ; Vincent, Tiffaney L ; Gill, Saar ; Nunez-Cruz, Selene ; Teachey, David T ; June, Carl H ; Milone, Michael C ; Chukinas, John A ; Shestova, Olga ; Aplenc, Richard ; Shen, Feng ; Miao, Fei

Many hematologic malignancies are not curable with chemotherapy and require novel therapeutic approaches. Chimeric antigen receptor (CAR) T-cell therapy is 1 such approach that involves the transfer of T cells engineered to express CARs for a specific cell-surface antigen. CD38 is a validated tumor antigen in multiple myeloma (MM) and T-cell acute lymphoblastic leukemia (T-ALL) and is also overexpressed in acute myeloid leukemia (AML). Here, we developed human CD38-redirected T cells (CART-38) as a unified approach to treat 3 different hematologic malignancies that occur across the pediatric-to-adult age spectrum. Importantly, CD38 expression on activated T cells did not impair CART-38 cells expansion or in vitro function. In xenografted mice, CART-38 mediated the rejection of AML, T-ALL, and MM cell lines and primary samples and prolonged survival. In a xenograft model of normal human hematopoiesis, CART-38 resulted in the expected reduction of hematopoietic progenitors, which warrants caution and careful monitoring of this potential toxicity when translating this new immunotherapy into the clinic. Deploying CART-38 against multiple CD38-expressing malignancies is significant because it expands the potential for this novel therapy to affect diverse patient populations.

01 Dec 2021·Journal of Hematology & Oncology

CD38-directed CAR-T cell therapy: a novel immunotherapy strategy for relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation

Letter

Author: Kang, Liqing ; Dai, Haiping ; Yu, Lei ; Li, Zheng ; Xu, Nan ; Liu, Tianhui ; Song, Baoquan ; Tang, Xiaowen ; Cui, Wei ; Yin, Jia ; Wu, Depei ; Cui, Qingya ; Zhu, Xiaming ; Zhu, Mingqing ; Shen, Wenhong ; Qian, Chongsheng ; Qu, Changju

AbstractAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acute myeloid leukemia (AML). However, most patients experience relapse after allo-HSCT, with a poor prognosis, and treatment options are limited. The lack of an ideal targetable antigen is a major obstacle for treating patients with relapsed AML. CD38 is known to be expressed on most AML and myeloma cells, and its lack of expression on hematopoietic stem cells (HSCs) renders it a potential therapeutic target for relapsed AML. To investigate the clinical therapeutic efficacy and safety of CD38-targeted chimeric antigen receptor T (CAR-T-38) cells, we enrolled 6 AML patients who experienced relapse post-allo-HSCT (clinicaltrials.gov: NCT04351022). Prior to CAR-T-38 treatment, the blasts in the bone marrow of these patients exhibited a median of 95% (92–99%) CD38 positivity. Four weeks after the initial infusion of CAR-T-38 cells, four of six (66.7%) patients achieved complete remission (CR) or CR with incomplete count recovery (CRi); the median CR or CRi time was 191 (range 117–261) days. The cumulative relapse rate at 6 months was 50%. The median overall survival (OS) and leukemia-free survival (LFS) times were 7.9 and 6.4 months, respectively. One case relapsed 117 days after the first CAR-T-38 cell infusion, with remission achieved after the second CAR-T-38 cell infusion. All six patients experienced clinically manageable side effects. In addition, multiparameter flow cytometry (FCM) revealed that CAR-T-38 cells eliminated CD38 positive blasts without off-target effects on monocytes and lymphocytes. Although this prospective study has a limited number of cases and a relatively short follow-up time, our preliminary data highlight the clinical utility and safety of CAR-T-38 cell therapy in treating relapsed AML post-allo-HSCT.

100 Deals associated with CART-38(Medical College of Soochow University)

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Indication	Highest Phase	Country/Location	Organization	Date
Acute Myeloid Leukemia	Phase 2	CN	Medical College of Soochow University	-

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