(1) Geng F (2) Dong L (3) Bao X (4) Guo Q (5) Guo J (6) Zhou Y (7) Yu B (8) Wu H (9) Wu J (10) Zhang H (11) Yu X (12) Kong W

Molecular therapy oncolytics | Free PMC Article

In this study, we investigate the synergistic effect of gemcitabine (Gem) and a novel DNA vaccine in the treatment of pancreatic cancer in mice and explore the anti-tumor mechanism of this combination therapy. Fibroblast activation protein _-expressing cancer-associated fibroblasts (FAP_(+) CAFs), a dominant component of the tumor microenvironment (TME), have been shown to modulate the extracellular matrix (ECM) to promote the growth, invasion, and metastasis of pancreatic cancer (PC). Therefore, FAP_(+) CAFs may be an ideal target for the treatment of PC. However, treatments that solely target FAP_(+) CAFs do not directly affect tumor cells. We recently constructed a novel chimeric DNA vaccine (OsFS) against human FAP_ and survivin, which simultaneously targets FAP_(+) CAFs and tumor cells. In Panc02 tumor-bearing mice, OsFS vaccination not only reduced the proportion of immunosuppressive cells but also promoted the recruitment of tumor-infiltrating lymphocytes, which remodeled the TME to support anti-tumor immune responses. Furthermore, after depletion of regulatory T cells (Tregs) by metronomic low-dose Gem therapy, the anti-tumor effects of OsFS were enhanced. Taken together, our results indicate that the combination of the FAP_/survivin co-targeting DNA vaccine and low-dose Gem may be an effective therapy for PC.

Author Info: (1) National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun 130012, P.R. China. (2) National Engineering Lab

Author Info: (1) National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun 130012, P.R. China. (2) National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun 130012, P.R. China. (3) National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun 130012, P.R. China. (4) National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun 130012, P.R. China. (5) National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun 130012, P.R. China. (6) National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun 130012, P.R. China. (7) National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun 130012, P.R. China. (8) National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun 130012, P.R. China. (9) National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun 130012, P.R. China. (10) National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun 130012, P.R. China. (11) National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun 130012, P.R. China. Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, P.R. China. (12) National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, No. 2699, Street Qianjin, Changchun 130012, P.R. China. Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, P.R. China.

Citation: Mol Ther Oncolytics 2022 Sep 15 26:304-313 Epub07/31/2022

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/36090474

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