Annihilation of Non-small Cell Lung Cancer by NKG2D CAR-T Cells Produced from T Cells from Peripheral Blood of Healthy Donors

被引:3
作者
Jiang, Jinhong [1 ,3 ]
Liu, Yonghua [1 ]
Zeng, Yuxiao [1 ]
Fang, Bingmu [1 ]
Chen, Yongping [2 ,4 ]
机构
[1] Wenzhou Med Univ, Affiliated Hosp 6, Lishui, Peoples R China
[2] Wenzhou Med Univ, Wenzhou, Peoples R China
[3] Wenzhou Med Univ, Affiliated Hosp 6, 15 Dazhong St, Lishui 323000, Peoples R China
[4] Wenzhou Med Univ, High Educ Pk,Chashan St, Wenzhou 325000, Peoples R China
关键词
non-small cell lung cancer; CAR-T cells; solid tumor; NKG2D-NKG2DL signaling; antitumor effect; RECEPTOR; LIGANDS; COSTIMULATION; PROGRESS; ROLES;
D O I
10.1089/jir.2023.0043
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Some progress has been made in immunotherapy with chimeric antigen receptor (CAR)-T cells targeting NKG2D-NKG2DL with the purpose of eradicating solid tumors. Non-small cell lung cancer (NSCLC) has been shown to express NKG2DL. This study hence evaluated the therapeutic effect of NKG2D CAR-T cells on NSCLC. Accordingly, NKG2D CAR-T cells were obtained from diverse human autologous T cell sources. T cells from peripheral blood T lymphocytes of healthy volunteers (without NKG2D CAR insertion) were used as NT-T cells. Coculture of effector cells (CAR-T cells or NT-T cells) with target cells (NSCLC cells such as PC-9 or NCL-H460 cells) was performed at different ratios. The cytotoxicity of CAR-T cells was examined using lactate dehydrogenase assay kits. Murine xenograft assay was conducted to investigate the in vivo antitumor effect of CAR-T cells. Cytokines secreted from CAR-T cells were assessed by enzyme-linked immunosorbent assay. CAR-T cell infiltration into xenografts was observed through immunochemical assay. Based on the results, NKG2DL was highly expressed in NSCLC cells. Compared with NT-T cells, NKG2D CAR-T cells from different sources of T cells delivered stronger toxicity, and secreted more effector and memory function-related cytokines to NSCLC cells, and those from the peripheral blood of healthy donors (H-T cells) exhibited the strongest effect. Furthermore, compared with NT-T cells, H-T cells and NKG2D CAR-T cells from NSCLC patients' peripheral blood diminished tumor, improved survival, increased body weight and tumor-infiltrating capacity, and upregulated serum IFN-gamma level in NOG mice. Collectively speaking, NKG2D CAR-T cells exhibit a robust effect on eradicating NSCLC in a NKG2DL-dependent manner, thus making themselves a promising therapeutic candidate for NSCLC patients.
引用
收藏
页码:445 / 454
页数:10
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