Engineering a HER2-CAR-NK Cell Secreting Soluble Programmed Cell Death Protein with Superior Antitumor Efficacy
文献类型：期刊论文
| 作者 | Xia, Wenjiao3; Chen, Jiaxin3; Hou, Wenqing3; Chen, Junsheng3; Xiong, Ying2; Li, Hongyan3; Qi, Xin3; Xu, Hui1; Xie, Zuoquan1 ; Li, Mingfeng3
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| 刊名 | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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| 出版日期 | 2023-04-01 |
| 卷号 | 24期号:7页码:6843 |
| 关键词 | breast cancers cytotherapy chimeric antigen receptor NK cells sPD-1 |
| DOI | 10.3390/ijms24076843 |
| 文献子类 | Article |
| 英文摘要 | A new therapy strategy for relapsing patients who have received trastuzumab treatment urgently needs to be explored. HER2-specific chimeric antigen receptor (CAR)-expressing NK cells are being rapidly developed for solid tumor therapy, as they have many advantages over HER2-CAR-T cells. Endogenous soluble PD-1 (sPD-1) from the PD-1 extracellular domain blocks PD-1/PD-L1 interaction to promote cancer immunology. Herein, we engineered a new HER2-CAR-NK cell that co-expresses sPD-1 (designed as sPD-1-CAR-NK cells) and assessed its cytotoxic activities toward various cancer cells, activation of immunity and sPD-1 release in vitro and in mouse models bearing breast cancer cells with high HER2 expression, with or without trastuzumab resistance. We demonstrated that sPD-1-CAR-NK cells were able to release bioactive sPD-1, thereby enhancing the cytolytic activities of HER2-CAR-NK cells against HER2 and PD-L1 highly expressing target cells accompanied by increases in the secretion of perforin, granzyme B and IFN-?. In vivo, sPD-1-CAR-NK cells had superior immunological anticancer efficacy compared to HER2-CAR-NK cells, and they had advantages over HER2-CAR-NK cells in the intraperitoneal injection of sPD-1. Moreover, the infiltration and activation of NK and T cells into tumor tissue were increased in mice with sPD-1-CAR-NK cells. There was no significant change in the body temperature, organ tissue and body weight in all groups except for the group with the PD-1 injection. Together, these data indicate that HER2-specific sPD-1-CAR-NK cells can transport sPD-1 into cancer tissues with high HER2 expression, further improving the efficacy of HER-CAR-NK cells without obvious side effects. sPD-1-CAR-NK is a promising cytotherapeutic agent for patients bearing HER2-positive breast cancer, including those with trastuzumab resistance. |
| WOS关键词 | BREAST-CANCER ; NK CELLS ; PD-1 ; INHIBITION ; RESPONSES ; PATIENT ; GROWTH ; LINE ; FC |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000969686800001 |
| 出版者 | MDPI |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309659]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Li, Jing |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 200126, Peoples R China 2.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China; 3.Ocean Univ China, Sch Med & Pharm, Key Lab Marine Drugs, Chinese Minist Educ,Lab Marine Drugs & Bioprod,Qin, Qingdao 266003, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Xia, Wenjiao,Chen, Jiaxin,Hou, Wenqing,et al. Engineering a HER2-CAR-NK Cell Secreting Soluble Programmed Cell Death Protein with Superior Antitumor Efficacy[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2023,24(7):6843. |
| APA | Xia, Wenjiao.,Chen, Jiaxin.,Hou, Wenqing.,Chen, Junsheng.,Xiong, Ying.,...&Li, Jing.(2023).Engineering a HER2-CAR-NK Cell Secreting Soluble Programmed Cell Death Protein with Superior Antitumor Efficacy.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,24(7),6843. |
| MLA | Xia, Wenjiao,et al."Engineering a HER2-CAR-NK Cell Secreting Soluble Programmed Cell Death Protein with Superior Antitumor Efficacy".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 24.7(2023):6843. |
入库方式： OAI收割
来源：上海药物研究所
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