Antitumor Study of Neoantigen-reactive T Cells Co-expressing IL-7 and CCL19 
in Mouse Lung Cancer

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 microenvironment, the therapeutic effect of NRT in solid tumors is limited. In this study, we designed NRT c...

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Bibliographic Details
Published in:Zhongguo fei ai za zhi 2024-07, Vol.27 (7), p.504-513
Main Authors: Wu, Di, Li, Chenhui, Wang, Yan, He, Zhengqiang, Jin, Chang'e, Guo, Min, Chen, Rongchang, Zhou, Chengzhi
Format: Article
Language:Chinese
Subjects:
Animals
Antigens
Antigens, Neoplasm - genetics
Antigens, Neoplasm - immunology
Carcinoma, Lewis Lung - genetics
Carcinoma, Lewis Lung - immunology
Carcinoma, Lewis Lung - therapy
ccl19
Cell Line, Tumor
Cell Proliferation
Chemokine CCL19 - genetics
Chemokine CCL19 - immunology
Chemokines
Cytokines
Dendritic cells
Enzymes
Female
Flow cytometry
Genes
Growth factors
Humans
il-7
Immunotherapy
Interleukin-7 - genetics
Interleukin-7 - immunology
Kinases
Ligands
Lung cancer
lung neoplasms
Lung Neoplasms - genetics
Lung Neoplasms - immunology
Lung Neoplasms - therapy
Lymphocytes
Mice
Mice, Inbred C57BL
neoantigens
nrt
Polymerase chain reaction
T cell receptors
T-Lymphocytes - immunology
Tumors
Vaccines
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Summary: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 microenvironment, 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. 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 expressed, and 7×19 NRT was successfully obtained. The anti-tumor effect was evaluated in vivo and in vitro in mice. The 7×19 NRT cells significantly enhanced the proliferation and invasion ability of T cells by secreting IL-7 and CCL
ISSN:1009-3419
1999-6187
1999-6187
DOI:10.3779/j.issn.1009-3419.2024.106.18