Rational design of innate defense regulator peptides as tumor vaccine adjuvants

Abstract The development of adjuvants has been an empirical process. Efforts to develop a new design and evaluation system for novel adjuvants are not only desirable but also necessary. Moreover, composite adjuvants that contain two or more types of adjuvants to synergistically enhance the immune re...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yaomei Tian, Qiuyue Hu, Rui Zhang, Bailing Zhou, Daoyuan Xie, Yuanda Wang, Xueyan Zhang, Li Yang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/e782e8939a9043a99db29cbb390a8f0f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e782e8939a9043a99db29cbb390a8f0f
record_format	dspace
spelling	oai:doaj.org-article:e782e8939a9043a99db29cbb390a8f0f2021-12-02T15:45:20ZRational design of innate defense regulator peptides as tumor vaccine adjuvants10.1038/s41541-021-00334-32059-0105https://doaj.org/article/e782e8939a9043a99db29cbb390a8f0f2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00334-3https://doaj.org/toc/2059-0105Abstract The development of adjuvants has been an empirical process. Efforts to develop a new design and evaluation system for novel adjuvants are not only desirable but also necessary. Moreover, composite adjuvants that contain two or more types of adjuvants to synergistically enhance the immune response are important for adjuvant and vaccine design. Innate defense regulator peptides (IDRs) are promising adjuvants for clinical immunotherapy because they exhibit multifaceted immunomodulatory capabilities. However, the rational design and discovery of IDRs that have improved immunomodulatory activities have been hampered by the lack of screening techniques and the great challenges in the identification of their interaction partners. Here, we describe a screening and evaluation system for IDR design. On the basis of in vitro screening, the optimized IDR DP7 recruited neutrophils, monocytes and macrophages to the site of infection. The adjuvant, comprising the DP7 and CpG oligonucleotide (CpG), induced chemokine/cytokine expression, enhanced the antigen uptake by dendritic cells and upregulated surface marker expression in dendritic cells. Vaccination with the NY-ESO-1 or OVA antigens combined with the adjuvant alum/CpG/DP7 strongly suppressed tumor growth in mice which was due to the improvement of antigen-specific humoral and cellular immunity. Regarding the mechanism of action, GPR35 may be the potential interaction partner of DP7. Our study revealed the potential application of the screening and evaluation system as a strategy for rationally designing effective IDRs or composite adjuvants and identifying their mechanism of action.Yaomei TianQiuyue HuRui ZhangBailing ZhouDaoyuan XieYuanda WangXueyan ZhangLi YangNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yaomei Tian Qiuyue Hu Rui Zhang Bailing Zhou Daoyuan Xie Yuanda Wang Xueyan Zhang Li Yang Rational design of innate defense regulator peptides as tumor vaccine adjuvants
description	Abstract The development of adjuvants has been an empirical process. Efforts to develop a new design and evaluation system for novel adjuvants are not only desirable but also necessary. Moreover, composite adjuvants that contain two or more types of adjuvants to synergistically enhance the immune response are important for adjuvant and vaccine design. Innate defense regulator peptides (IDRs) are promising adjuvants for clinical immunotherapy because they exhibit multifaceted immunomodulatory capabilities. However, the rational design and discovery of IDRs that have improved immunomodulatory activities have been hampered by the lack of screening techniques and the great challenges in the identification of their interaction partners. Here, we describe a screening and evaluation system for IDR design. On the basis of in vitro screening, the optimized IDR DP7 recruited neutrophils, monocytes and macrophages to the site of infection. The adjuvant, comprising the DP7 and CpG oligonucleotide (CpG), induced chemokine/cytokine expression, enhanced the antigen uptake by dendritic cells and upregulated surface marker expression in dendritic cells. Vaccination with the NY-ESO-1 or OVA antigens combined with the adjuvant alum/CpG/DP7 strongly suppressed tumor growth in mice which was due to the improvement of antigen-specific humoral and cellular immunity. Regarding the mechanism of action, GPR35 may be the potential interaction partner of DP7. Our study revealed the potential application of the screening and evaluation system as a strategy for rationally designing effective IDRs or composite adjuvants and identifying their mechanism of action.
format	article
author	Yaomei Tian Qiuyue Hu Rui Zhang Bailing Zhou Daoyuan Xie Yuanda Wang Xueyan Zhang Li Yang
author_facet	Yaomei Tian Qiuyue Hu Rui Zhang Bailing Zhou Daoyuan Xie Yuanda Wang Xueyan Zhang Li Yang
author_sort	Yaomei Tian
title	Rational design of innate defense regulator peptides as tumor vaccine adjuvants
title_short	Rational design of innate defense regulator peptides as tumor vaccine adjuvants
title_full	Rational design of innate defense regulator peptides as tumor vaccine adjuvants
title_fullStr	Rational design of innate defense regulator peptides as tumor vaccine adjuvants
title_full_unstemmed	Rational design of innate defense regulator peptides as tumor vaccine adjuvants
title_sort	rational design of innate defense regulator peptides as tumor vaccine adjuvants
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e782e8939a9043a99db29cbb390a8f0f
work_keys_str_mv	AT yaomeitian rationaldesignofinnatedefenseregulatorpeptidesastumorvaccineadjuvants AT qiuyuehu rationaldesignofinnatedefenseregulatorpeptidesastumorvaccineadjuvants AT ruizhang rationaldesignofinnatedefenseregulatorpeptidesastumorvaccineadjuvants AT bailingzhou rationaldesignofinnatedefenseregulatorpeptidesastumorvaccineadjuvants AT daoyuanxie rationaldesignofinnatedefenseregulatorpeptidesastumorvaccineadjuvants AT yuandawang rationaldesignofinnatedefenseregulatorpeptidesastumorvaccineadjuvants AT xueyanzhang rationaldesignofinnatedefenseregulatorpeptidesastumorvaccineadjuvants AT liyang rationaldesignofinnatedefenseregulatorpeptidesastumorvaccineadjuvants
_version_	1718385782342811648

Rational design of innate defense regulator peptides as tumor vaccine adjuvants

Ejemplares similares