title: Plant-produced trastuzumab inhibits the growth of HER2 positive cancer cells.
abstract: To study the agricultural production of biosimilar antibodies, trastuzumab (Herceptin) was expressed in Nicotiana benthamiana using the magnICON viral-based transient expression system. Immunoblot analyses of crude plant extracts revealed that trastuzumab accumulates within plants mostly in the fully assembled tetrameric form. Purification of trastuzumab from N. benthamiana was achieved using a scheme that combined ammonium sulfate precipitation with affinity chromatography. Following purification, the specificity of the plant-produced trastuzumab for the HER2 receptor was compared with Herceptin and confirmed by western immunoblot. Functional assays revealed that plant-produced trastuzumab and Herceptin have similar in vitro antiproliferative effects on breast cancer cells that overexpress HER2. Results confirm that plants may be developed as an alternative to traditional antibody expression systems for the production of therapeutic mAbs.
authors.affiliation: School of Environmental Sciences, University of Guelph, 50 Stone Road East, Guelph, Ontario N1G 2W1, Canada.
authors.forename: Brittany M
authors.initials: BM
authors.lastname: Grohs
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Niu
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Veldhuis
authors.forename: Salma
authors.initials: S
authors.lastname: Trabelsi
authors.forename: Freydoun
authors.initials: F
authors.lastname: Garabagi
authors.forename: John A
authors.initials: JA
authors.lastname: Hassell
authors.forename: Michael D
authors.initials: MD
authors.lastname: McLean
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Hall
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology*; D019149:Bioreactors; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D046549:Plantibodies / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D030821:Plants, Genetically Modified / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D014026:Nicotiana / Q000235:genetics / Q000378:metabolism*; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D046549:Plantibodies; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human