Abstract:
:Although current demands for therapeutic mAbs are growing quickly, production methods to date, including in vitro mammalian tissue culture and transgenic animals, provide only limited quantities at high cost. Several tumor-associated antigens in tumor cells have been identified as targets for therapeutic mAbs. Here we describe the production of mAb BR55-2 (IgG2a) in transgenic plants that recognizes the nonprotein tumor-associated antigen Lewis Y oligosaccharide overexpressed in human carcinomas, particularly breast and colorectal cancers. Heavy and light chains of mAb BR55-2 were expressed separately and assembled in plant cells of low-alkaloid tobacco transgenic plants (Nicotiana tabacum cv. LAMD609). Expression levels of plant-derived mAb (mAbP) were high (30 mg/kg of fresh leaves) in T1 generation plants. Like the mammalian-derived mAbM, the plant mAbP bound specifically to both SK-BR3 breast cancer cells and SW948 colorectal cancer cells. The Fc domain of both mAbP and mAbM showed the similar binding to FcgammaRI receptor (CD64). Comparable levels of cytotoxicity against SK-BR3 cells were also shown for both mAbs in antibody-dependent cell-mediated cytotoxicity assay. Furthermore, plant-derived BR55-2 efficiently inhibited SW948 tumor growth xenografted in nude mice. Altogether, these findings suggest that mAbP originating from low-alkaloid tobacco exhibit biological activities suitable for efficient immunotherapy.
journal_name
Proc Natl Acad Sci U S Aauthors
Brodzik R,Glogowska M,Bandurska K,Okulicz M,Deka D,Ko K,van der Linden J,Leusen JH,Pogrebnyak N,Golovkin M,Steplewski Z,Koprowski Hdoi
10.1073/pnas.0603043103subject
Has Abstractpub_date
2006-06-06 00:00:00pages
8804-9issue
23eissn
0027-8424issn
1091-6490pii
0603043103journal_volume
103pub_type
杂志文章abstract::Most small multicopy antibiotic-resistance plasmids of Staphylococcus aureus contain a major axis of hyphenated dyad symmetry (palA) that is required for normal replication and stability, although located outside of the minimal replicon. Rearrangements affecting palA cause plasmid instability, a marked reduction in co...
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