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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
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.
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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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