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A single local delivery of paclitaxel and nucleic acids via an immunoactive polymer eliminates solid tumors and induces systemic antitumor immunity

ABSTRACT: Despite recent advances in cancer therapy, hard-to-reach, unidentified tumors remain a significant clinical challenge. A promising approach is to treat locatable and accessible tumors locally and stimulate antitumor immunity in situ to exert systemic effects against distant tumors. We hypothesize that a local carrier of immunotherapeutics is critical to the effective activation of in-situ antitumor immunity. Here, we develop a polyethyleneimine derivative (2E’), which activates immune cells and co-delivers hydrophobic immunogenic cell death inducers and immunomodulatory nucleic acids/nucleotides. A single local administration of 2E’ or its combination with paclitaxel and PD-L1 siRNA or cyclic dinucleotide induces strong antitumor immunity, resulting in immediate regression of large established tumors, tumor-free survival, and the resistance to rechallenge and metastasis in different models. This study supports that effective in-situ induction of antitumor immunity can lead to systemic protection from distant and recurrent diseases, where 2E’ plays multiple roles as a simple and versatile carrier of immunotherapeutics.

ORGANISM(S): Mus musculus

PROVIDER: GSE178971 | GEO | 2022/05/19

REPOSITORIES: GEO

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