EXO and PagL Protect Murin Against Breast Cancer

Exosomes (EXO) are a cellular vehicles used for cancer immunotherapy due to their immuneinducing properties. To identify whether designed structure based on tumoral EXO have acytotoxic effect together with a potent immunological property, we synthesized a novelstructure based on EXO and modified LPS (PagL) and surveyed its cytostatic effect a murinetumor model. A new recombinant structure made up of two components, exosomes (EXO)and modified LPS (PagL) that believed can be an appropriate candidate in tumorimmunotherapy. EXO were purified from tumor cells and modified LPS was puirifed fromrecombinant clone. Modified LPS was added with exosomes and was used for immunizationof mice before being challenged with 4T1 cells. Tumor size, survival time, necrosis,metastasis rate, and the level of IL-4, IL-17, TNF-α and IFN-γ were measured. Immunizationof the mice with PagL or EXO increased the stimulation index of lymphocytes significantlycompared with the PBS (p<0.01). In addition, there was a significant increase of TNF-α andIFN-γ secreted from isolated splenocyts of the mice immunized by either PagL or EXO incomparison with PBS (p<0. 01 and p<0.05, respectively). The level of IL-17 and IFN- γamong mice immunized with PagL was significantly lower than PBS-treated group (p<0.05).PagL immunization relatively prolonged the survival of the mice, and had inhibitory impact ontumor size. Pathologic manifestations showed the significant rise of necrosis afterimmunization with PagL compared to PBS (p<0.01). Overall, our findings suggest that thepresence of PagL decreased the tumorigenesis compared to EXO+PagL and boosts theantitumor immunity.

Keywords:

Exosome , Modified LPS , Immunotherapy , Breast Cancer , 4T1 Cells