分泌PD-1阻断抗体的EGLIF-CAR-T细胞显著介导胃癌的消除。
EGLIF-CAR-T Cells Secreting PD-1 Blocking Antibodies Significantly Mediate the Elimination of Gastric Cancer.
作者信息
Zhou Jing-Tao, Liu Jiang-Hao, Song Ting-Ting, Ma Bo, Amidula Nuermaimait, Bai Chao
机构信息
General Surgery, The Seventh Affiliated Hospital of Xinjiang Medical University, Urumqi, People's Republic of China.
General Surgery, Xinjiang Uygur Autonomous Region Eighth People's Hospital, Urumqi, People's Republic of China.
出版信息
Cancer Manag Res. 2020 Sep 23;12:8893-8902. doi: 10.2147/CMAR.S260915. eCollection 2020.
OBJECTIVE
To investigate the anti-tumor effects of programmed cell death protein 1 (PD-1) scFv-secreting EGFR-chimeric antigen receptor-modified (CAR)-T cells against gastric cancer.
METHODS
Second-generation EGFR-CAR-T cells and fourth-generation PD-1 scFv-secreting EGFR-CAR-T cells were engineered. The anti-tumor activities of chimeric antigen receptor-modified (CAR)-T cells were analyzed in vitro by long-term co-culture with gastric cancer cells. The tumor scavenging capacity in vivo was evaluated in xenograft and PDX mouse models.
RESULTS
EGFR-CAR-T cells secreting PD-1 scFv showed enhanced long-term tumor cell killing capacity in vitro. These cells also showed significant anti-tumor effect in the subcutaneous xenograft model of gastric cancer as well as in the PDX model, and autocrine PD-1 antibody secretion significantly increased tumor infiltration of the CAR-T cells.
CONCLUSION
EGFR-CAR-T cells secreting PD-1 scFv are highly effective against gastric cancer and offer new insights into anti-cancer immunotherapy.
目的
研究分泌程序性细胞死亡蛋白1（PD-1）单链抗体片段（scFv）的表皮生长因子受体（EGFR）嵌合抗原受体修饰的（CAR）-T细胞对胃癌的抗肿瘤作用。
方法
构建第二代EGFR-CAR-T细胞和分泌第四代PD-1 scFv的EGFR-CAR-T细胞。通过与胃癌细胞长期共培养，体外分析嵌合抗原受体修饰的（CAR）-T细胞的抗肿瘤活性。在异种移植和人源肿瘤组织异种移植（PDX）小鼠模型中评估体内肿瘤清除能力。
结果
分泌PD-1 scFv的EGFR-CAR-T细胞在体外显示出增强的长期肿瘤细胞杀伤能力。这些细胞在胃癌皮下异种移植模型以及PDX模型中也显示出显著的抗肿瘤作用，并且自分泌PD-1抗体显著增加了CAR-T细胞的肿瘤浸润。
结论
分泌PD-1 scFv的EGFR-CAR-T细胞对胃癌高度有效，并为抗癌免疫治疗提供了新的见解。
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