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Induced CD20 Expression on B-Cell Malignant Cells Heightened the Cytotoxic Activity of Chimeric Antigen Receptor

Yingxi Xu1, Saisai Li1, Ying Wang1

  • 1State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.

Human Gene Therapy
|November 2, 2018
PubMed

CD20 is an effective immunotherapy target for CD20+ B-cell malignant cells. Monoclonal antibody, especially rituximab, has been a conventional strategy in the treatment of B-cell malignancies such as non-Hodgkin's lymphoma. However, treatment with monoclonal antibodies has not been enough to overcome the refractory/relapse problems. Chimeric antigen receptor engineered T (CAR-T) cells have exhibited excellent therapeutic effect on lymphocytic leukemia in recent years. In this study, a CD20-specific CAR was constructed and the cytotoxic efficacy of CD20 CAR-T cells on B-cell malignant cells was evaluated by CD107a degranulation, pro-inflammation cytokine production, and true lytic ability in vitro and in vivo. It was found that CD20 CAR-T cells possessed stronger cytotoxic ability against CD20 highly expressed cells. Furthermore, when histone deacetylase inhibitor was used to enhance the expression of CD20 antigen on the surface of B-cell malignant cells via inducing acetylation of H3K9 on CD20 promoter site, it revealed that the cytotoxicity of CD20 CAR-T cells against histone deacetylase inhibitor-treated B-cell malignant cells was significantly enhanced.

Keywords:
B-cell malignanciesCD20HDAC inhibitorImmunotherapychimeric antigen receptor

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