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

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...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2021-02, Vol.11 (1), p.4625-13, Article 4625
Main Authors: Hamamichi, Shusei, Fukuhara, Takeshi, Umeda, Izumi O., Fujii, Hirofumi, Hattori, Nobutaka
Format: Article
Language:English
Subjects:
631/61/54
631/61/54/152
Animals
Antibodies - immunology
Antigen-Antibody Complex
Antigens
Antigens, CD - immunology
Cell Line, Tumor
Cytotoxicity
Doxorubicin
Doxorubicin - chemistry
Drug delivery
Humanities and Social Sciences
Humans
Immunotoxins
Internalization
Liposomes
Mice
Mice, Inbred BALB C
Monoclonal antibodies
multidisciplinary
Receptors, Transferrin - immunology
Science
Science (multidisciplinary)
Side effects
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-84043-w