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

Abstract

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.

• Authors: Qianqian Ni, Fuwu Zhang, Yijing Liu, Zhantong Wang, Guocan Yu, Brian Liang, Gang Niu, Ting Su, Guizhi Zhu, Guangming Lu, Longjiang Zhang, Xiaoyuan Chen
• Journal: Science advances (Sci Adv) Vol. 6 Issue 12 Pg. eaaw6071 (03 2020) ISSN: 2375-2548 [Electronic] United States
• PMID: 32206706 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Chemical References

• Adjuvants, Immunologic
• Antigens, Neoplasm
• Antineoplastic Agents, Immunological
• Cancer Vaccines
• Pdcd1 protein, mouse
• Programmed Cell Death 1 Receptor

Topics

• Adjuvants, Immunologic
• Animals
• Antigen Presentation (immunology)
• Antigens, Neoplasm (immunology)
• Antineoplastic Agents, Immunological (pharmacology)
• Cancer Vaccines (administration & dosage, immunology)
• Colorectal Neoplasms (immunology, pathology, therapy)
• Combined Modality Therapy
• Dendritic Cells (immunology, metabolism)
• Disease Models, Animal
• Humans
• Immunogenicity, Vaccine
• Immunotherapy (methods)
• Mice
• Nanoparticles (chemistry, ultrastructure)
• Nanotechnology
• Programmed Cell Death 1 Receptor (antagonists & inhibitors)
• T-Lymphocytes (drug effects, immunology, metabolism)
• Theranostic Nanomedicine
• Xenograft Model Antitumor Assays