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Am J Cancer Res. 2019 Jan 1;9(1):64-78. eCollection 2019.

A novel CD7 chimeric antigen receptor-modified NK-92MI cell line targeting T-cell acute lymphoblastic leukemia.

You F1,2,3, Wang Y3, Jiang L3, Zhu X4, Chen D1,2,3, Yuan L5, An G1,2, Meng H1,2, Yang L1,2,6,3.

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The Cyrus Tang Hematology Center, Soochow University Suzhou, Jiangsu, P. R. China.
Collaborative Innovation Center of Hematology, Soochow University Suzhou, Jiangsu, P. R. China.
PersonGen BioTherapeutics (Suzhou) Co., Ltd. P. R. China.
Department of Hematology, Central Laboratory, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine Nanjing, P. R. China.
Department of Hematology, Peking University Third Hospital Beijing, P. R. China.
State Key Laboratory of Radiation Medicine and Protection, Soochow University Suzhou, Jiangsu, P. R. China.


Chimeric antigen receptor (CAR) immunotherapy has recently shown promise in clinical trials for B-cell malignancies; however, designing CARs for T-cell based diseases remain a challenge since most target antigens are shared between normal and malignant cells, leading to CAR-T cell fratricide. CD7 is highly expressed in T-cell acute lymphoblastic leukemia (T-ALL), but it is not expressed in one small group of normal T lymphocytes. Here, we constructed monovalent CD7-CAR-NK-92MI and bivalent dCD7-CAR-NK-92MI cells using the CD7 nanobody VHH6 sequences from our laboratory. Both CD7-CAR-NK-92MI and dCD7-CAR-NK-92MI cells consistently showed specific and potent anti-tumor activity against T-cell leukemia cell lines and primary tumor cells. We observed robust cytotoxicity of the bivalent mdCD7-CAR-NK-92MI monoclonal cells against primary T-ALL samples. In agreement with the enhanced cytotoxicity of mdCD7-CAR-NK-92MI cells, significant elevations in the secretion of Granzyme B and interferon γ (IFN-γ) were also found in mdCD7-CAR-NK-92MI cells in response to CD7-positive primary T-ALL cells compared with NK-92MI-mock cells. Furthermore, we also demonstrated that mdCD7-CAR-NK-92MI cells significantly inhibited disease progression in xenograft mouse models of T-ALL primary tumor cells. Our data suggest that CD7-CAR-NK-92MI cells can be used as a new method or a complementary therapy for treating T-cell acute lymphocytic leukemia.


American type culture collection; CD7; NK-92MI; T-cell acute lymphoblastic leukemia; chimeric antigen receptor


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