In situ chemoimmunotherapy hydrogel elicits immunogenic cell death and evokes efficient antitumor immune response

原位化学免疫治疗水凝胶引发免疫原性细胞死亡并激发有效的抗肿瘤免疫反应

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作者:Qin Liu, Rui Xu, Jingwen Shen, Yaping Tao, Jingyi Shao, Yaohua Ke, Baorui Liu

Background

Chemoimmunotherapy has shown promising advantages of eliciting immunogenic cell death and activating anti-tumor immune responses. However, the systemic toxicity of chemotherapy and tumor immunosuppressive microenvironment limit the clinical application.

Conclusions

Our strategy provides a novel insight into the combination of chemotherapy and immunotherapy and has the potential for clinical translation.

Methods

Here, an injectable sodium alginate hydrogel (ALG) loaded with nanoparticle albumin-bound-paclitaxel (Nab-PTX) and an immunostimulating agent R837 was developed for local administration. Two murine hepatocellular carcinoma and breast cancer models were established. The tumor-bearing mice received the peritumoral injection of R837/Nab-PTX/ALG once a week for two weeks. The antitumor efficacy, the immune response, and the tumor microenvironment were investigated.

Results

This chemoimmunotherapy hydrogel with sustained-release character was proven to have significant effects on killing tumor cells and inhibiting tumor growth. Peritumoral injection of our hydrogel caused little harm to normal organs and triggered a potent antitumor immune response against both hepatocellular carcinoma and breast cancer. In the tumor microenvironment, enhanced immunogenic cell death induced by the combination of Nab-PTX and R837 resulted in 3.30-fold infiltration of effector memory T cells and upregulation of 20 biological processes related to immune responses. Conclusions: Our strategy provides a novel insight into the combination of chemotherapy and immunotherapy and has the potential for clinical translation.

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