靶向叶酸受体α的7x19嵌合抗原受体T细胞抑制小鼠三阴性乳腺癌异种移植模型
Folate Receptor-Alpha Targeted 7x19 CAR-T Suppressed Triple-Negative Breast Cancer Xenograft Model in Mice.
作者信息
Ye Xueshuai, Deng Xinna, Wen Junye, Li Yang, Zhang Mengya, Cai Ziqi, Liu Guan, Wang Hezhi, Cai Jianhui
机构信息
Department of Surgery, Hebei Medical University, Shijiazhuang 050051, Hebei Province, China.
Department of Oncology & Surgery, Hebei General Hospital, Shijiazhuang 050051, Hebei Province, China.
出版信息
J Oncol. 2022 Mar 7;2022:2112898. doi: 10.1155/2022/2112898. eCollection 2022.
BACKGROUND
Triple-negative breast cancer (TNBC) is the worst prognosis subtype of breast cancer due to lack of specific targets. Recent studies have shown that immunotherapy may solve that problem by targeting folate receptor-alpha (FR).
METHODS
Gene modified T cells were manufactured to express FRa specific chimeric antigen receptor (FRa CAR) and secrete interleukin-7 (IL-7) and chemokine C-C motif ligand 19 (CCL19). CAR-T cells that secrete IL-7 and CCL19 (7 × 19 CAR-T) were evaluated for their antitumor activity both in vitro and in vivo.
RESULTS
7 × 19 CAR-T showed remarkable antitumor activity in vitro. Combined with PBMC, 7 × 19 CAR-T inhibited TNBC xenograft model growth superiorly compared with single-application or conventional CAR-T cells. Histopathological analyses showed increased DC or T cells infiltration to tumor tissues.
CONCLUSION
Taken together, our results showed that 7 × 19 CAR-T have remarkable anti-TNBC tumor activity and showed a broad application prospect in the treatment of incurable TNBC patients.
背景
三阴性乳腺癌（TNBC）是乳腺癌中预后最差的亚型，因为缺乏特异性靶点。最近的研究表明，免疫疗法可能通过靶向叶酸受体-α（FR）来解决这一问题。
方法
制备基因修饰的T细胞，使其表达FRα特异性嵌合抗原受体（FRα CAR）并分泌白细胞介素-7（IL-7）和趋化因子C-C基序配体19（CCL19）。对分泌IL-7和CCL19的CAR-T细胞（7×19 CAR-T）的体外和体内抗肿瘤活性进行评估。
结果
7×19 CAR-T在体外显示出显著的抗肿瘤活性。与外周血单核细胞（PBMC）联合使用时，7×19 CAR-T比单次应用或传统CAR-T细胞更能有效地抑制TNBC异种移植模型的生长。组织病理学分析显示肿瘤组织中树突状细胞（DC）或T细胞浸润增加。
结论
综上所述，我们的结果表明7×19 CAR-T具有显著的抗TNBC肿瘤活性，在治疗无法治愈的TNBC患者方面显示出广阔的应用前景。
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