Abstract：
:Anti-cytokine therapeutic antibodies have been demonstrated to be effective in the treatment of several auto-immune disorders. However, The problems in antibody manufacture and the immunogenicity caused by multiple doses of antibodies inspire people to use auto-cytokine as immunogen to induce anti-cytokine antibodies. Nevertheless, the tolerance for inducing immune response against self-antigen has hindered the wide application of the strategy. To overcome the tolerance, here we proposed a strategy using the inter-species cytokine as immunogen for active immunization (TISCAI) to induce anti-cytokine antibody. As a proof of concept, an inter-species cytokine RANKL was successfully used as immunogen to induce anti-RANKL immune response. Furthermore, to prevent undesirable side-effects, the human RANKL was mutated based on the crystal structure of the complex of human RANKL and its rodent counterpart receptor RANK. We found, the antibodies produced blocked the osteoclast development in vitro and osteoporosis in OVX rat models. The results demonstrated this strategy adopted is very useful for general anti-cytokine immunotherapy for different diseases settings.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Liu C,Zhao Y,He W,Wang W,Chen Y,Zhang S,Ma Y,Gohda J,Ishida T,Walter TS,Owens RJ,Stuart DI,Ren J,Gao Bdoi
10.1038/srep14150subject
Has Abstractpub_date
2015-09-28 00:00:00pages
14150issn
2045-2322pii
srep14150journal_volume
5pub_type
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