The recombinant chimeric antibody chHAb18 against hepatocellular carcinoma can be produced in milk of transgenic mice
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ORIGINAL PAPER
The recombinant chimeric antibody chHAb18 against hepatocellular carcinoma can be produced in milk of transgenic mice Jingjing Wei • Xiangmin Yang • Min Zheng Meili Wang • Yunping Dai • Zhinan Chen • Ning Li
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Received: 17 February 2010 / Accepted: 21 May 2010 / Published online: 12 June 2010 Ó Springer Science+Business Media B.V. 2010
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 J. Wei Y. Dai N. Li (&) State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100094, China e-mail: [email protected] X. Yang Z. Chen Department of Cell Biology & Cell Engineering Research Centre, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi’an 710032, China e-mail: [email protected] M. Zheng M. Wang Beijing Genprotein Biotechnology Company, Beijing, China
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. Keywords Hepatocellular carcinoma Chimeric monoclonal antibody Expression Transgenic mice Milk Abbreviations HCC Hepatocellular carcinoma mAb Monoclonal antibody HC Heavy chain LC Light chain ELISA Enzyme-linked immunosorbent assay
Introduction Human hepatocellular carcinoma (HCC) is a major health problem worldwide, with an estimated incidence ranging between 500,000 and 1,000,000 new cases annually (Lau and Lai 2008). It is the fifth most common cancer in the world, and the third leading cause of cancer-related death (Thomas 2008). Of the therapies aimed at a cure, liver resection and
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transplantation in combination with radiotherapy and/ or chemotherapy remains the best choice for HCC patients (Lau and Lai 2007). However, there is no effective treatment for advanced unresectable tumors or metastatic or recurrent tumors (Ortega et al. 1991), and conventional treatment with cytotoxic drugs is not selective
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