Novel method for screening functional antibody with comprehensive analysis of its immunoliposome

Abstract Development of monoclonal antibody is critical for targeted drug delivery because its characteristics determine improved therapeutic efficacy and reduced side-effect. Antibody therapeutics target surface molecules; hence, internalization is desired for drug delivery. As an antibody–drug con...

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Autores principales:	Shusei Hamamichi, Takeshi Fukuhara, Izumi O. Umeda, Hirofumi Fujii, Nobutaka Hattori
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d9f5ce5c0da9457b98a2f13055a3a5c7
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spelling	oai:doaj.org-article:d9f5ce5c0da9457b98a2f13055a3a5c72021-12-02T13:34:46ZNovel method for screening functional antibody with comprehensive analysis of its immunoliposome10.1038/s41598-021-84043-w2045-2322https://doaj.org/article/d9f5ce5c0da9457b98a2f13055a3a5c72021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84043-whttps://doaj.org/toc/2045-2322Abstract Development of monoclonal antibody is critical for targeted drug delivery because its characteristics determine improved therapeutic efficacy and reduced side-effect. Antibody therapeutics target surface molecules; hence, internalization is desired for drug delivery. As an antibody–drug conjugate, a critical parameter is drug-to-antibody ratio wherein the quantity of drugs attached to the antibody influences the antibody structure, stability, and efficacy. Here, we established a cell-based immunotoxin screening system to facilitate the isolation of functional antibodies with internalization capacities, and discovered an anti-human CD71 monoclonal antibody. To overcome the limitation of drug-to-antibody ratio, we employed the encapsulation capacity of liposome, and developed anti-CD71 antibody-conjugated liposome that demonstrated antigen–antibody dependent cellular uptake when its synthesis was optimized. Furthermore, anti-CD71 antibody-conjugated liposome encapsulating doxorubicin demonstrated antigen–antibody dependent cytotoxicity. In summary, this study demonstrates the powerful pipeline to discover novel functional antibodies, and the optimal method to synthesize immunoliposomes. This versatile technology offers a rapid and direct approach to generate antibodies suitable for drug delivery modalities.Shusei HamamichiTakeshi FukuharaIzumi O. UmedaHirofumi FujiiNobutaka HattoriNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shusei Hamamichi Takeshi Fukuhara Izumi O. Umeda Hirofumi Fujii Nobutaka Hattori Novel method for screening functional antibody with comprehensive analysis of its immunoliposome
description	Abstract Development of monoclonal antibody is critical for targeted drug delivery because its characteristics determine improved therapeutic efficacy and reduced side-effect. Antibody therapeutics target surface molecules; hence, internalization is desired for drug delivery. As an antibody–drug conjugate, a critical parameter is drug-to-antibody ratio wherein the quantity of drugs attached to the antibody influences the antibody structure, stability, and efficacy. Here, we established a cell-based immunotoxin screening system to facilitate the isolation of functional antibodies with internalization capacities, and discovered an anti-human CD71 monoclonal antibody. To overcome the limitation of drug-to-antibody ratio, we employed the encapsulation capacity of liposome, and developed anti-CD71 antibody-conjugated liposome that demonstrated antigen–antibody dependent cellular uptake when its synthesis was optimized. Furthermore, anti-CD71 antibody-conjugated liposome encapsulating doxorubicin demonstrated antigen–antibody dependent cytotoxicity. In summary, this study demonstrates the powerful pipeline to discover novel functional antibodies, and the optimal method to synthesize immunoliposomes. This versatile technology offers a rapid and direct approach to generate antibodies suitable for drug delivery modalities.
format	article
author	Shusei Hamamichi Takeshi Fukuhara Izumi O. Umeda Hirofumi Fujii Nobutaka Hattori
author_facet	Shusei Hamamichi Takeshi Fukuhara Izumi O. Umeda Hirofumi Fujii Nobutaka Hattori
author_sort	Shusei Hamamichi
title	Novel method for screening functional antibody with comprehensive analysis of its immunoliposome
title_short	Novel method for screening functional antibody with comprehensive analysis of its immunoliposome
title_full	Novel method for screening functional antibody with comprehensive analysis of its immunoliposome
title_fullStr	Novel method for screening functional antibody with comprehensive analysis of its immunoliposome
title_full_unstemmed	Novel method for screening functional antibody with comprehensive analysis of its immunoliposome
title_sort	novel method for screening functional antibody with comprehensive analysis of its immunoliposome
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d9f5ce5c0da9457b98a2f13055a3a5c7
work_keys_str_mv	AT shuseihamamichi novelmethodforscreeningfunctionalantibodywithcomprehensiveanalysisofitsimmunoliposome AT takeshifukuhara novelmethodforscreeningfunctionalantibodywithcomprehensiveanalysisofitsimmunoliposome AT izumioumeda novelmethodforscreeningfunctionalantibodywithcomprehensiveanalysisofitsimmunoliposome AT hirofumifujii novelmethodforscreeningfunctionalantibodywithcomprehensiveanalysisofitsimmunoliposome AT nobutakahattori novelmethodforscreeningfunctionalantibodywithcomprehensiveanalysisofitsimmunoliposome
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Novel method for screening functional antibody with comprehensive analysis of its immunoliposome

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