Antitumor Study of Neoantigen-reactive T Cells Co-expressing IL-7 and CCL19 in Mouse Lung Cancer
10.3779/j.issn.1009-3419.2024.106.18
- VernacularTitle:共表达IL-7/CCL19的新抗原反应性T细胞对小鼠肺癌的抗肿瘤研究
- Author:
WU DI
1
;
LI CHENHUI
;
WANG YAN
;
HE ZHENGQIANG
;
JIN CHANG'E
;
GUO MIN
;
CHEN RONGCHANG
;
ZHOU CHENGZHI
Author Information
1. 518020 深圳,暨南大学第二临床医学院(深圳市人民医院)深圳市呼吸疾病研究所肺重症医学科,南方科技大学第一附属医院(深圳市人民医院)
- Keywords:
Neoantigens;
IL-7;
CCL19;
Lung neoplasms;
NRT
- From:
Chinese Journal of Lung Cancer
2024;27(7):504-513
- CountryChina
- Language:Chinese
-
Abstract:
Background and objective Neoantigen reactive T cell(NRT)has the ability to inhibit the growth of tumors expressing specific neoantigens.However,due to the difficult immune infiltration and the inhibition of tumor micro en-vironment,the therapeutic effect of NRT in solid tumors is limited.In this study,we designed NRT cells(7×19 NRT)that can express both interleukin-7(IL-7)and chemokine C-C motif ligand 19(CCL19)in mouse lung cancer cells,and evaluated the difference in anti-tumor effect between 7×19 NRT cells and conventional NRT cells.Methods We performed next-generation sequencing and neoantigen prediction for mouse Lewis lung carcinoma(LLC),prepared RNA vaccine,cultured NRT cells,constructed retroviral vectors encoding IL-7 and CCL19,transduced NRT cells and IL-7 and CCL19 were successfully ex-pressed,and 7×19 NRT was successfully obtained.The anti-tumor effect was evaluated in vivo and in vitro in mice.Results The 7×19 NRT cells significantly enhanced the proliferation and invasion ability of T cells by secreting IL-7 and CCL19,achieved significant tumor inhibition in the mouse lung cancer and extended the survival period of mice.The T cell infiltration into tumor tissue and the necrosis of tumor tissue increased significantly after 7×19 NRT treatment.In addition,both 7×19 NRT treatment and conventional NRT treatment were safe.Conclusion The anti-solid tumor ability of NRT cells is significantly enhanced by the arming of IL-7 and CCL19,which is a safe and effective genetic modification of NRT.
