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In situ vaccination with biocompatibility controllable immuno-sensitizer inducing antitumor immunity
1Center for Photomedicine, Department of Biotechnology, The Catholic University of Korea, 43 Jibongro, Wonmi-gu, Bucheon-si, Gyeonggi do, 14662, Republic of Korea.
Anticancer immunotherapy is emerging as a promising tumor treatment that can replace the conventional tumor treatment such as surgery, radiation and chemo drug, but its therapeutic effect against solid tumor is limited due to the tumor microenvironment (TME). Herein, to overcome this limitation, the biocompatibility controllable immuno-sensitizer (BCI) based on polyethylene imine that can be applied to solid tumors is developed. BCI accumulates in the tumors by EPR effect and induces in situ tumor destruction that convert tumors into antigen source by biocompatibility change through surface charge switching in response to the acidic TME. Generated tumor antigens promote the maturation of dendritic cells and recruitment of cytotoxic T cells in tumors. Results from in vitro and in vivo experiments reveal that the BCI effectively induces tumor destruction and antitumor immune response. In consequence, the synergic effect of in situ tumor destruction and antitumor immune response induced by BCI's biocompatibility conversion remarkably enhances immunotherapeutic effect. This study may provide a way to improve immunotherapeutic effect on solid tumors by demonstrating the therapeutic effect of BCI against solid tumor and suggest a platform to control the toxicity of cationic polymer for the its extended biomedical application.
Anticancer immunotherapy is emerging as a promising tumor treatment that can replace the conventional tumor treatment such as surgery, radiation and chemo drug, but its therapeutic effect against solid tumor is limited due to the tumor microenvironment (TME). Herein, to overcome this limitation, the biocompatibility controllable immuno-sensitizer (BCI) based on polyethylene imine that can be applied to solid tumors is developed. BCI accumulates in the tumors by EPR effect and induces in situ tumor destruction that convert tumors into antigen source by biocompatibility change through surface charge switching in response to the acidic TME. Generated tumor antigens promote the maturation of dendritic cells and recruitment of cytotoxic T cells in tumors. Results from in vitro and in vivo experiments reveal that the BCI effectively induces tumor destruction and antitumor immune response. In consequence, the synergic effect of in situ tumor destruction and antitumor immune response induced by BCI's biocompatibility conversion remarkably enhances immunotherapeutic effect. This study may provide a way to improve immunotherapeutic effect on solid tumors by demonstrating the therapeutic effect of BCI against solid tumor and suggest a platform to control the toxicity of cationic polymer for the its extended biomedical application.
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