eISSN: 1644-4124
ISSN: 1426-3912
Central European Journal of Immunology
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1/2023
vol. 48
 
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abstract:
Experimental immunology

Immunotherapy of B cell lymphoma with CD22-redirected CAR NK-92 cells

Xiaopeng Tian
1
,
Ruixi Zhang
2
,
Huimin Qin
1
,
Xiangru Shi
1
,
Wenhui Qi
1
,
Dongpeng Jiang
1
,
Tingting Zhu
1
,
Aining Sun
1

  1. National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Institute of Blood and Marrow Transplantation, Medical College of Soochow University, Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, Soochow University, China
  2. Henan Key Laboratory of Coronary Heart Disease Control, Central China Fuwai Hospital, China
Cent Eur J Immunol 2023; 48 (1): 1-13
DOI: https://doi.org/10.5114/ceji.2023.126672
Online publish date: 2023/04/14
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Introduction:
Chimeric antigen receptor (CAR)-NK cells are considered safer than CAR-T cells due to their short lifetime and production of lower toxicity cytokines. By virtue of unlimited proliferative ability in vitro, NK-92 cells could be utilized as the source for CAR-engineered NK cells. CD22 is highly expressed in B cell lymphoma. The goal of our study was to determine whether CD22 could become an alternative target for CAR-NK-92 therapy against B cell lymphoma.

Material and methods:
We first generated m971-BBZ NK-92 that expressed a CAR for binding CD22 in vitro. The expression of CAR was assessed by flow cytometric analysis as well as immunoblotting. The cytotoxicity of the m971-BBZ NK-92 cells towards target lymphoma cells was determined by the luciferase-based cytolysis assay. The production of cytokines in CAR NK-92 cells in response to target cells was evaluated by ELISA assay. Lastly, the cytolytic effect was evaluated by the cytolysis assay mentioned above following irradiation. The level of inhibitory receptor of CAR-expressing cells was assessed by flow cytometry.

Results:
CD22-specific CAR was expressed on m971-BBZ NK-92 cells successfully. m971-BBZ NK-92 cells efficiently lysed CD22-expressing lymphoma cells and produced large amounts of cytokines after coculture with target cells. Meanwhile, irradiation did not apparently influence the cytotoxicity of m971-BBZ NK-92 cells. Inhibitory receptor detection exhibited a lower level of PD-1 in m971-BBZ NK-92 cells than FMC-63 BBZ T cells after repeated antigen stimulation.

Conclusions:
Our data show that adoptive transfer of m971-BBZ NK-92 could serve as a promising strategy for immunotherapy of B cell lymphoma

keywords:

CAR-NK, CD22, NK-92, B cell lymphoma, immunotherapy

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