Attenuated Salmonella Carrying IL-21-siRNA-CCR2 Co-expression Plasmid Enhances Anti-tumor Immune Response in Lung Cancer-bearing Mice

Title:Attenuated Salmonella Carrying IL-21-siRNA-CCR2 Co-expression Plasmid Enhances Anti-tumor Immune Response in Lung Cancer-bearing Mice

Volume: 25

Author(s): Jing Li, Kun Li, Jinhua Yang, Mingyu Mo, Bingran Han, Jinwei Chen, Jiaxin Geng, Mengyu Lei, Pengfei Chen, Mingguang Shao, Hanyu Jiang, Tiesuo Zhao, Huijie Jia*Wei Wang

Affiliation:

• Xinxiang Engineering Technology Research Center of Immune Checkpoint Drug for Liver-Intestinal Tumors, Xinxiang Medical University, Xinxiang, Henan, China

Keywords: Lung cancer, IL-21, siRNA, CCR2, immunotherapy.

Abstract:

Introduction: There is an urgent and ongoing need to develop effective therapeutic strategies for lung cancer. CCR2 is considered a valid target for lung cancer treatment. However, singletarget- oriented monotherapy frequently fails to yield satisfactory results, and multi-target therapy has become the current trend. IL-21 exerts anti-tumor effects across various cancers, including lung cancer. Whether the combination of CCR2-targeted therapy and IL-21 exerts a stronger anti-tumor effect remains to be verified.

Methods: Mouse Lewis lung cancer cells and pre-constructed IL-21-siRNA-CCR2 plasmid were used. Annexin V-FITC, flow cytometry, Western blot, Ki67 IHC, immunofluorescence, and TUNEL assay were used to analyze apoptosis, immune cells, proteins, and proliferation.

Results: Compared with single-agent treatments, combination treatment significantly inhibited CCR2 expression, enhanced IL-21 expression, and slowed tumor growth in mouse lung cancer tissues. Further analysis demonstrated that this treatment effectively increased the infiltration of CD4⁺ and CD8⁺ T lymphocytes in tumor tissues, elevated the proportion of M1 macrophages while reducing that of M2 macrophages, and notably increased the percentages of CD4+ T lymphocytes and NK cells in mouse spleens.

Discussion: The combination treatment not only directly suppressed the proliferation of tumor cells but also enhanced the overall anti-tumor immune response in tumor-bearing mice. In subsequent studies, it will be further verified that the efficacy of this treatment is in a variety of tumor cell lines.

Conclusion: The combination of IL-21 and CCR2 blockade exerts a synergistic anti-lung-cancer effect.

Cite this article as:

Li Jing, Li Kun, Yang Jinhua, Mo Mingyu, Han Bingran, Chen Jinwei, Geng Jiaxin, Lei Mengyu, Chen Pengfei, Shao Mingguang, Jiang Hanyu, Zhao Tiesuo, Jia Huijie*, Wang Wei, Attenuated Salmonella Carrying IL-21-siRNA-CCR2 Co-expression Plasmid Enhances Anti-tumor Immune Response in Lung Cancer-bearing Mice, Current Gene Therapy 2025; 25 () . https://dx.doi.org/10.2174/0115665232407110251015103908