A bi-adjuvant nanovaccine that potentiates immunogenicity of neoantigen for combination immunotherapy of colorectal cancer
Menée in vitro et à l'aide d'un modèle murin de cancer colorectal, cette étude met en évidence l'intérêt d'un nanovaccin délivrant un peptide dérivé de la glucokinase Adpgk et deux adjuvants, l'imidazoquinoléine R848 (un agoniste des récepteurs TLR/7/8) et un polynucléotide à motifs CpG (un agoniste des récepteurs TLR9), pour accroître l'immunogénicité des néoantigènes tumoraux et améliorer la réponse à une immunothérapie anti-PD-1
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.
Science Advances 2020