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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.

Author information

1
The Cyrus Tang Hematology Center, Soochow University Suzhou, Jiangsu, P. R. China.
2
Collaborative Innovation Center of Hematology, Soochow University Suzhou, Jiangsu, P. R. China.
3
PersonGen BioTherapeutics (Suzhou) Co., Ltd. P. R. China.
4
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.
5
Department of Hematology, Peking University Third Hospital Beijing, P. R. China.
6
State Key Laboratory of Radiation Medicine and Protection, Soochow University Suzhou, Jiangsu, P. R. China.

Abstract

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.

KEYWORDS:

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

PMID:
30755812
PMCID:
PMC6356925

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