Document Detail


Comparative in vitro and experimental in vivo studies of the anti-epidermal growth factor receptor antibody nimotuzumab and its aglycosylated form produced in transgenic tobacco plants.
MedLine Citation:
PMID:  23046448     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
A broad variety of foreign genes can be expressed in transgenic plants, which offer the opportunity for large-scale production of pharmaceutical proteins, such as therapeutic antibodies. Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) recombinant IgG1 antibody approved in different countries for the treatment of head and neck squamous cell carcinoma, paediatric and adult glioma, and nasopharyngeal and oesophageal cancers. Because the antitumour mechanism of nimotuzumab is mainly attributed to its ability to interrupt the signal transduction cascade triggered by EGF/EGFR interaction, we have hypothesized that an aglycosylated form of this antibody, produced by mutating the N(297) position in the IgG(1) Fc region gene, would have similar biochemical and biological properties as the mammalian-cell-produced glycosylated counterpart. In this paper, we report the production and characterization of an aglycosylated form of nimotuzumab in transgenic tobacco plants. The comparison of the plantibody and nimotuzumab in terms of recognition of human EGFR, effect on tyrosine phosphorylation and proliferation in cells in response to EGF, competition with radiolabelled EGF for EGFR, affinity measurements of Fab fragments, pharmacokinetic and biodistribution behaviours in rats and antitumour effects in nude mice bearing human A431 tumours showed that both antibody forms have very similar in vitro and in vivo properties. Our results support the idea that the production of aglycosylated forms of some therapeutic antibodies in transgenic plants is a feasible approach when facing scaling strategies for anticancer immunoglobulins.
Authors:
Meilyn Rodríguez; Lincidio Pérez; Jorge V Gavilondo; Greta Garrido; Mónica Bequet-Romero; Ignacio Hernández; Vivian Huerta; Gleysin Cabrera; Marlene Pérez; Osmani Ramos; René Leyva; Mariela León; Pedro Luis Ramos; Ada Triguero; Abel Hernández; Belinda Sánchez; Marta Ayala; Jeny Soto; Ernesto González; Osmani Mendoza; Kenia Tiel; Merardo Pujol
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-10
Journal Detail:
Title:  Plant biotechnology journal     Volume:  -     ISSN:  1467-7652     ISO Abbreviation:  Plant Biotechnol. J.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101201889     Medline TA:  Plant Biotechnol J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors Plant Biotechnology Journal © 2012 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.
Affiliation:
Center for Genetic Engineering and Biotechnology (CIGB), Playa, Havana, Cuba.
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