Localized cocktail chemoimmunotherapy after in situ gelation to trigger robust systemic antitumor immune responses
Yu Chao, Chao Liang, Huiquan Tao, Yaran Du, Di Wu, Ziliang Dong, Qiutong Jin, Guobin Chen, Jun Xu, Zhisheng Xiao, Qian Chen, Chao Wang, Jian Chen, Zhuang Liu
Abstract
Currently, there is a huge demand to develop chemoimmunotherapy with reduced systemic toxicity and potent efficacy to combat late-stage cancers with spreading metastases. Here, we report several "cocktail" therapeutic formulations by mixing immunogenic cell death (ICD)-inducing chemotherapeutics and immune adjuvants together with alginate (ALG) for localized chemoimmunotherapy. Immune checkpoint blockade (ICB) antibody may be either included into this cocktail for local injection or used via conventional intravenous injection. After injection of such cocktail into a solid tumor, in-situ gelation of ALG would lead to local retention and sustained release of therapeutics to reduce systemic toxicity. The chemotherapy-induced ICD with the help of immune adjuvant would trigger tumor-specific immune responses, which are further amplified by ICB to elicit potent systemic antitumor immune responses in destructing local tumors, eliminating metastases and inhibiting cancer recurrence. Our strategy of combining clinically used agents for tumor-localized cocktail chemoimmunotherapy possesses great potential for clinical translation.