CAFs/肿瘤细胞共靶向 DNA 疫苗联合低剂量吉西他滨治疗 Panc02 小鼠胰腺癌

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 α-expressing cancer-associated fibroblasts (FAPα + 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, FAPα + CAFs may be an ideal target for the treatment of PC.

However, treatments that solely target FAPα + CAFs do not directly affect tumor cells.

We recently constructed a novel chimeric DNA vaccine (OsFS) against human FAPα and survivin, which simultaneously targets FAPα + 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 FAPα/survivin co-targeting DNA vaccine and low-dose Gem may be an effective therapy for PC.