A giant step forward: chimeric antigen receptor T-cell therapy for lymphoma
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A giant step forward: chimeric antigen receptor T-cell therapy for lymphoma Houli Zhao1,2,3, Yiyun Wang1,2,3, Elaine Tan Su Yin1,2,3, Kui Zhao4, Yongxian Hu (
✉)1,2,3, He Huang (✉)1,2,3
1
Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China; Zhejiang Province Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou 310000, China; 3Institute of Hematology, Zhejiang University, Hangzhou 310000, China; 4PET-CT Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310000, China 2
© The Author(s) 2020. This article is published with open access at link.springer.com and journal.hep.com.cn 2020
Abstract The combination of the immunotherapy (i.e., the use of monoclonal antibodies) and the conventional chemotherapy increases the long-term survival of patients with lymphoma. However, for patients with relapsed or treatment-resistant lymphoma, a novel treatment approach is urgently needed. Chimeric antigen receptor T (CAR-T) cells were introduced as a treatment for these patients. Based on recent clinical data, approximately 50% of patients with relapsed or refractory B-cell lymphoma achieved complete remission after receiving the CD19 CAR-T cell therapy. Moreover, clinical data revealed that some patients remained in remission for more than two years after the CAR-T cell therapy. Other than the CD19-targeted CAR-T, the novel target antigens, such as CD20, CD22, CD30, and CD37, which were greatly expressed on lymphoma cells, were studied under preclinical and clinical evaluations for use in the treatment of lymphoma. Nonetheless, the CAR-T therapy was usually associated with potentially lethal adverse effects, such as the cytokine release syndrome and the neurotoxicity. Therefore, optimizing the structure of CAR, creating new drugs, and combining CAR-T cell therapy with stem cell transplantation are potential solutions to increase the effectiveness of treatment and reduce the toxicity in patients with lymphoma after the CAR-T cell therapy. Keywords chimeric antigen receptor T (CAR-T) cell; lymphoma; cytokine release syndrome (CRS); immune effector cellassociated neurotoxicity syndrome (ICANS)
Introduction The lymphoma comprises a heterogeneous group of lymphoid neoplasms, which originate from lymphocytes, and arises in the context of immune dysregulation. Generally, the lymphoma is divided into two subtypes, namely, Hodgkin lymphomas (HL) and non-Hodgkin lymphomas (NHL) in accordance with the morphology of tumor cells. The HL is characterized using the Reed– Sternberg cells, which are derived from B cells [1]. The NHL is derived from diverse cell types, including B, T, or natural killer (NK) cells. In 2019, newly diagnosed HL and NHL account for 0.46% and 4.21% of cases, respectively, in the United States [2]. In China, the incidence rate of
Received December 3, 2019; accepted June 3, 2020 Correspondence: He Huang, [email protected]; Yongxian Hu, [email protected]
malignant lymphoma i
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