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Multifunctional Protein Conjugates with Built-in Adjuvant (Adjuvant-Protein-Antigen) as Cancer Vaccines Boost Potent Immune Responses
Many cancer vaccines are not successful in clinical trials, mainly due to the challenges associated with breaking immune tolerance. Herein, we report a new strategy using an adjuvant-protein-antigen (three-in-one protein conjugates with built-in adjuvant) as an anticancer vaccine, in which both the...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063246/ https://www.ncbi.nlm.nih.gov/pubmed/32146328 http://dx.doi.org/10.1016/j.isci.2020.100935 |
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author | Du, Jing-Jing Wang, Chang-Wei Xu, Wen-Bo Zhang, Lian Tang, Yuan-Kai Zhou, Shi-Hao Gao, Xiao-Fei Yang, Guang-Fu Guo, Jun |
author_facet | Du, Jing-Jing Wang, Chang-Wei Xu, Wen-Bo Zhang, Lian Tang, Yuan-Kai Zhou, Shi-Hao Gao, Xiao-Fei Yang, Guang-Fu Guo, Jun |
author_sort | Du, Jing-Jing |
collection | PubMed |
description | Many cancer vaccines are not successful in clinical trials, mainly due to the challenges associated with breaking immune tolerance. Herein, we report a new strategy using an adjuvant-protein-antigen (three-in-one protein conjugates with built-in adjuvant) as an anticancer vaccine, in which both the adjuvant (small-molecule TLR7 agonist) and tumor-associated antigen (mucin 1, MUC1) are covalently conjugated to the same carrier protein (BSA). It is shown that the protein conjugates with built-in adjuvant can increase adjuvant's stimulation, prevent adjuvant's systemic toxicities, facilitate the codelivery of adjuvants and antigens, and enhance humoral and cellular immune responses. The IgG antibody titers elicited by the self-adjuvanting three-in-one protein conjugates were significantly higher than those elicited by the vaccine mixed with TLR7 agonist (more than 15-fold) or other traditional adjuvants. Importantly, the potent immune responses against cancer cells suggest that this new vaccine construct is an effective strategy for the personalized antitumor immunotherapy. |
format | Online Article Text |
id | pubmed-7063246 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-70632462020-03-16 Multifunctional Protein Conjugates with Built-in Adjuvant (Adjuvant-Protein-Antigen) as Cancer Vaccines Boost Potent Immune Responses Du, Jing-Jing Wang, Chang-Wei Xu, Wen-Bo Zhang, Lian Tang, Yuan-Kai Zhou, Shi-Hao Gao, Xiao-Fei Yang, Guang-Fu Guo, Jun iScience Article Many cancer vaccines are not successful in clinical trials, mainly due to the challenges associated with breaking immune tolerance. Herein, we report a new strategy using an adjuvant-protein-antigen (three-in-one protein conjugates with built-in adjuvant) as an anticancer vaccine, in which both the adjuvant (small-molecule TLR7 agonist) and tumor-associated antigen (mucin 1, MUC1) are covalently conjugated to the same carrier protein (BSA). It is shown that the protein conjugates with built-in adjuvant can increase adjuvant's stimulation, prevent adjuvant's systemic toxicities, facilitate the codelivery of adjuvants and antigens, and enhance humoral and cellular immune responses. The IgG antibody titers elicited by the self-adjuvanting three-in-one protein conjugates were significantly higher than those elicited by the vaccine mixed with TLR7 agonist (more than 15-fold) or other traditional adjuvants. Importantly, the potent immune responses against cancer cells suggest that this new vaccine construct is an effective strategy for the personalized antitumor immunotherapy. Elsevier 2020-02-24 /pmc/articles/PMC7063246/ /pubmed/32146328 http://dx.doi.org/10.1016/j.isci.2020.100935 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Du, Jing-Jing Wang, Chang-Wei Xu, Wen-Bo Zhang, Lian Tang, Yuan-Kai Zhou, Shi-Hao Gao, Xiao-Fei Yang, Guang-Fu Guo, Jun Multifunctional Protein Conjugates with Built-in Adjuvant (Adjuvant-Protein-Antigen) as Cancer Vaccines Boost Potent Immune Responses |
title | Multifunctional Protein Conjugates with Built-in Adjuvant (Adjuvant-Protein-Antigen) as Cancer Vaccines Boost Potent Immune Responses |
title_full | Multifunctional Protein Conjugates with Built-in Adjuvant (Adjuvant-Protein-Antigen) as Cancer Vaccines Boost Potent Immune Responses |
title_fullStr | Multifunctional Protein Conjugates with Built-in Adjuvant (Adjuvant-Protein-Antigen) as Cancer Vaccines Boost Potent Immune Responses |
title_full_unstemmed | Multifunctional Protein Conjugates with Built-in Adjuvant (Adjuvant-Protein-Antigen) as Cancer Vaccines Boost Potent Immune Responses |
title_short | Multifunctional Protein Conjugates with Built-in Adjuvant (Adjuvant-Protein-Antigen) as Cancer Vaccines Boost Potent Immune Responses |
title_sort | multifunctional protein conjugates with built-in adjuvant (adjuvant-protein-antigen) as cancer vaccines boost potent immune responses |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063246/ https://www.ncbi.nlm.nih.gov/pubmed/32146328 http://dx.doi.org/10.1016/j.isci.2020.100935 |
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