A bi-adjuvant nanovaccine that potentiates immunogenicity of neoantigen for combination immunotherapy of colorectal cancer
| Autor: | Brian Liang, Qianqian Ni, Fuwu Zhang, Gang Niu, Ting Su, Longjiang Zhang, Yijing Liu, Xiaoyuan Chen, Guangming Lu, Guocan Yu, Zhantong Wang, Guizhi Zhu |
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| Rok vydání: | 2019 |
| Předmět: |
Colorectal cancer
medicine.medical_treatment T-Lymphocytes Programmed Cell Death 1 Receptor 02 engineering and technology Theranostic Nanomedicine Mice Antineoplastic Agents Immunological Immunogenicity Vaccine Cancer immunotherapy Nanotechnology health care economics and organizations Research Articles Cancer 0303 health sciences Antigen Presentation Multidisciplinary integumentary system Immunogenicity food and beverages SciAdv r-articles 021001 nanoscience & nanotechnology Combined Modality Therapy 3. Good health Immunotherapy 0210 nano-technology Colorectal Neoplasms Adjuvant Research Article Agonist medicine.drug_class chemical and pharmacologic phenomena complex mixtures Cancer Vaccines 03 medical and health sciences Antigen Adjuvants Immunologic Antigens Neoplasm medicine Animals Humans Health and Medicine 030304 developmental biology business.industry TLR9 Dendritic Cells medicine.disease Xenograft Model Antitumor Assays Immune checkpoint Disease Models Animal Cancer research Nanoparticles business |
| Zdroj: | Science Advances |
| ISSN: | 2375-2548 |
| Popis: | A rationally designed bi-adjuvant nanovaccine enhances neoantigen immunogenicity and enables combination immunotherapy. 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. |
| Databáze: | OpenAIRE |
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