Self-Assembled Nanofibers Elicit Potent HPV16 E7-Specific Cellular Immunity And Abolish Established TC-1 Graft Tumor

Sijin Li,1–3 Qishu Zhang,1–3 Hongmei Bai,1–3 Weiwei Huang,1–3 Congyan Shu,1–3 Chao Ye,1–3 Wenjia Sun,1–3 Yanbing Ma1–3 1Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Science...

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Autores principales:	Li S, Zhang Q, Bai H, Huang W, Shu C, Ye C, Sun W, Ma Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	self-assembling nanofibers cellular immunity tumor vaccine Human papillomavirus (HPV) Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a3be9065859048318a8a90bc35269471
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spelling	oai:doaj.org-article:a3be9065859048318a8a90bc352694712021-12-02T09:46:26ZSelf-Assembled Nanofibers Elicit Potent HPV16 E7-Specific Cellular Immunity And Abolish Established TC-1 Graft Tumor1178-2013https://doaj.org/article/a3be9065859048318a8a90bc352694712019-10-01T00:00:00Zhttps://www.dovepress.com/self-assembled-nanofibers-elicit-potent-hpv16-e7-specific-cellular-imm-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Sijin Li,1–3 Qishu Zhang,1–3 Hongmei Bai,1–3 Weiwei Huang,1–3 Congyan Shu,1–3 Chao Ye,1–3 Wenjia Sun,1–3 Yanbing Ma1–3 1Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, People’s Republic of China; 2Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Disease, Kunming, People’s Republic of China; 3Yunnan Engineering Research Center of Vaccine Research and Development on Severe Infectious Disease, Kunming, People’s Republic of ChinaCorrespondence: Yanbing MaLaboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, 935 Jiaoling Road, Kunming 650118, People’s Republic of ChinaTel +86 871 6833 9287Fax +86 871 6833 4483Email yanbingma@126.comBackground: Vaccines are one of the most promising strategies for immunotherapy of HPV associated tumors; however, they generally lack significant clinical efficacy at present. This inefficacy might be due to inefficient generation of anti-tumor cellular immune responses.Purpose: This study aimed to assess the potential of using self-assembled nanofibers as a new vaccine platform to elicit potent HPV antigen - specific anti-tumor immunity.Methods: A HPV16 E744-62 peptide was chemically appended to the N terminus of self-assembling peptide Q11. The nanofibers were prepared and used to immunize mice through a preventive or therapeutic strategy in a TC-1 graft tumor model.Results: Preventive immunization with nanofibers almost completely suppressed the growth of primarily grafted TC-1 tumors and even a re-challenge of tumor cells after a six-week rest. Therapeutic immunization significantly increased the levels of effector Th1 cells, CTLs and the cytokines IFN-γ and TNF-α in E7 peptide-stimulated splenocytes, and the immunization reduced Th2, MDSC and IL-4 contents compared to the controls. The nanofiber immunization significantly suppressed the growth of established tumors and achieved 66.7% and 50% tumor-free in mice carrying 2–3 mm tumors and even larger tumors with a diameter of 5–6 mm respectively. In addition, the nanofibers were more efficient than the corresponding unassembled peptides for the treatment of established larger size tumors.Conclusion: The results indicated that self-assembling nanofibers could elicit robust HPV antigen -specific anti-tumor cellular immunity and are a potent antigen delivery system for HPV related tumor vaccines.Keywords: self-assembling nanofibers, cellular immunity, tumor, vaccine, human papillomavirus, HPVLi SZhang QBai HHuang WShu CYe CSun WMa YDove Medical Pressarticleself-assembling nanofiberscellular immunitytumorvaccineHuman papillomavirus (HPV)Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 8209-8219 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	self-assembling nanofibers cellular immunity tumor vaccine Human papillomavirus (HPV) Medicine (General) R5-920
spellingShingle	self-assembling nanofibers cellular immunity tumor vaccine Human papillomavirus (HPV) Medicine (General) R5-920 Li S Zhang Q Bai H Huang W Shu C Ye C Sun W Ma Y Self-Assembled Nanofibers Elicit Potent HPV16 E7-Specific Cellular Immunity And Abolish Established TC-1 Graft Tumor
description	Sijin Li,1–3 Qishu Zhang,1–3 Hongmei Bai,1–3 Weiwei Huang,1–3 Congyan Shu,1–3 Chao Ye,1–3 Wenjia Sun,1–3 Yanbing Ma1–3 1Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Science & Peking Union Medical College, Kunming, People’s Republic of China; 2Yunnan Key Laboratory of Vaccine Research & Development on Severe Infectious Disease, Kunming, People’s Republic of China; 3Yunnan Engineering Research Center of Vaccine Research and Development on Severe Infectious Disease, Kunming, People’s Republic of ChinaCorrespondence: Yanbing MaLaboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, 935 Jiaoling Road, Kunming 650118, People’s Republic of ChinaTel +86 871 6833 9287Fax +86 871 6833 4483Email yanbingma@126.comBackground: Vaccines are one of the most promising strategies for immunotherapy of HPV associated tumors; however, they generally lack significant clinical efficacy at present. This inefficacy might be due to inefficient generation of anti-tumor cellular immune responses.Purpose: This study aimed to assess the potential of using self-assembled nanofibers as a new vaccine platform to elicit potent HPV antigen - specific anti-tumor immunity.Methods: A HPV16 E744-62 peptide was chemically appended to the N terminus of self-assembling peptide Q11. The nanofibers were prepared and used to immunize mice through a preventive or therapeutic strategy in a TC-1 graft tumor model.Results: Preventive immunization with nanofibers almost completely suppressed the growth of primarily grafted TC-1 tumors and even a re-challenge of tumor cells after a six-week rest. Therapeutic immunization significantly increased the levels of effector Th1 cells, CTLs and the cytokines IFN-γ and TNF-α in E7 peptide-stimulated splenocytes, and the immunization reduced Th2, MDSC and IL-4 contents compared to the controls. The nanofiber immunization significantly suppressed the growth of established tumors and achieved 66.7% and 50% tumor-free in mice carrying 2–3 mm tumors and even larger tumors with a diameter of 5–6 mm respectively. In addition, the nanofibers were more efficient than the corresponding unassembled peptides for the treatment of established larger size tumors.Conclusion: The results indicated that self-assembling nanofibers could elicit robust HPV antigen -specific anti-tumor cellular immunity and are a potent antigen delivery system for HPV related tumor vaccines.Keywords: self-assembling nanofibers, cellular immunity, tumor, vaccine, human papillomavirus, HPV
format	article
author	Li S Zhang Q Bai H Huang W Shu C Ye C Sun W Ma Y
author_facet	Li S Zhang Q Bai H Huang W Shu C Ye C Sun W Ma Y
author_sort	Li S
title	Self-Assembled Nanofibers Elicit Potent HPV16 E7-Specific Cellular Immunity And Abolish Established TC-1 Graft Tumor
title_short	Self-Assembled Nanofibers Elicit Potent HPV16 E7-Specific Cellular Immunity And Abolish Established TC-1 Graft Tumor
title_full	Self-Assembled Nanofibers Elicit Potent HPV16 E7-Specific Cellular Immunity And Abolish Established TC-1 Graft Tumor
title_fullStr	Self-Assembled Nanofibers Elicit Potent HPV16 E7-Specific Cellular Immunity And Abolish Established TC-1 Graft Tumor
title_full_unstemmed	Self-Assembled Nanofibers Elicit Potent HPV16 E7-Specific Cellular Immunity And Abolish Established TC-1 Graft Tumor
title_sort	self-assembled nanofibers elicit potent hpv16 e7-specific cellular immunity and abolish established tc-1 graft tumor
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/a3be9065859048318a8a90bc35269471
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Self-Assembled Nanofibers Elicit Potent HPV16 E7-Specific Cellular Immunity And Abolish Established TC-1 Graft Tumor

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