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Boosting innate and adaptive antitumor immunity via a biocompatible and carrier-free nanovaccine engineered by the bisphosphonates-metal coordination

Mengmeng Qin,Minghui Li,Ge Song,Canyu Yang,Peiyao Wu,Wenbing Dai,Hua Zhang,Xueqing Wang,Yiguang Wang,Demin Zhou,Bing He,Qiang Zhang

Most of tumor vaccines currently focus on inducing adaptive immunity, while the antitumor potential of innate immunity is getting more attentions. In an attempt to recruit both innate and adaptive immunity, bisphosphonates (BPs) as a type of orthopaedics drugs with biosafety was applied in an antitumor vaccine here as an innate immune regulator. BPs and calcium themselves shaped the biodegradable nanocarrier via their coordination (CaBPs), which could load peptide antigens due to its hydrophilicity and be stabilized by surface lipids including a TLR4 agonist (nanovaccine). As results, the incorporation of BPs triggered the proliferation and activation of DCs and innate-like γδT cells, while the nanovaccine enhanced antigen presentation and specific lysis of tumor cells. The combination of nanovaccine and anti-PD-1 achieved a 50% total disappearance of tumor. In a prophylactic study, no any tumor occurred in nanovaccine group during a 110 day study with 3 time tumor challenges. Generally, this study validates the double antitumor immunities and provides a very promising approach for clinic application.