title: The recombinant chimeric antibody chHAb18 against hepatocellular carcinoma can be produced in milk of transgenic mice.
abstract: Biologically active recombinant monoclonal antibodies (mAbs) and their derivatives are in demand as therapeutic agents against a variety of cancers. The antibodies are generally produced by mammalian cell culture, but their production in the milk of transgenic animals would help meet the increasing demand. The mouse-human chimeric antibody chHAb18 has been proven to inhibit the invasion and metastasis of human hepatocellular carcinoma (HCC) cells by recognizing the HAb18G/CD147 molecule that is highly expressed on the surface of HCC tissue. Here, we report that transgenic mice generated by co-microinjection of two cassettes encoding the heavy and light chain genes of chHAb18 could highly express functional chHAb18 in their mammary glands. The expression level range of 1.1-7.4 mg ml(-1) was independent of transgenic copy number. Immunoassays demonstrated the ability and specificity of chHAb18 to bind purified antigen (i.e., HAb18G) or HCC cells. Recombinant chHAb18 from transgenic milk exhibited affinity almost equal to chHAb18 derived from CHO cells, and was 68% of that of the parental murine antibody, HAb18. In light of successful clinical application of HAb18, the chHAb18 expressed in mammary glands of transgenic mice constitutes an important step towards high-yield and scaled-up production of this antibody.
authors.affiliation: State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100094, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wei
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.forename: Meili
authors.initials: M
authors.lastname: Wang
authors.forename: Yunping
authors.initials: Y
authors.lastname: Dai
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Chen
authors.forename: Ning
authors.initials: N
authors.lastname: Li
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D058846:Antibodies, Monoclonal, Murine-Derived / Q000096:biosynthesis*; D000970:Antineoplastic Agents / Q000276:immunology / Q000378:metabolism; D051926:Basigin / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology; D008321:Mammary Glands, Animal / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008892:Milk / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D011993:Recombinant Fusion Proteins; D051926:Basigin