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Sci Adv. 2020 Mar 18;6(12):eaaw6071. doi: 10.1126/sciadv.aaw6071. eCollection 2020 Mar.

A bi-adjuvant nanovaccine that potentiates immunogenicity of neoantigen for combination immunotherapy of colorectal cancer.

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Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China.
Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, MD 20892, USA.
Department of Pharmaceutics, Center for Pharmaceutical Engineering and Sciences, Institute for Structural Biology, Drug Discovery and Development, School of Pharmacy; Massey Cancer Center; Virginia Commonwealth University, Richmond, VA, 23219, USA.


Neoantigen vaccines have been enthusiastically pursued for personalized cancer immunotherapy while vast majority of neoantigens have no or low immunogenicity. Here, a bi-adjuvant neoantigen nanovaccine (banNV) that codelivered a peptide neoantigen (Adpgk) with two adjuvants [Toll-like receptor (TLR) 7/8 agonist R848 and TLR9 agonist CpG] was developed for potent cancer immunotherapy. Specifically, banNVs were prepared by a nanotemplated synthesis of concatemer CpG, nanocondensation with cationic polypeptides, and then physical loading with hydrophobic R848 and Adpgk. The immunogenicity of the neoantigen was profoundly potentiated by efficient codelivery of neoantigen and dual synergistic adjuvants, which is accompanied by reduced acute systemic toxicity. BanNVs sensitized immune checkpoint programmed death receptor 1 (PD-1) on T cells, therefore, a combination of banNVs with aPD-1 conspicuously induced the therapy response and led to complete regression of 70% neoantigen-specific tumors without recurrence. We conclude that banNVs are promising to optimize personalized therapeutic neoantigen vaccines for cancer immunotherapy.

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