State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing, 100094, China.
Transgenic Res. 2011 Apr;20(2):321-30. doi: 10.1007/s11248-010-9408-3. Epub 2010 Jun 12.
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.
生物活性重组单克隆抗体（mAbs）及其衍生物是治疗各种癌症的有效药物。这些抗体通常通过哺乳动物细胞培养生产，但如果能在转基因动物的乳汁中生产，则有助于满足日益增长的需求。鼠人嵌合抗体 chHAb18 已被证明通过识别高度表达在 HCC 组织表面的 HAb18G/CD147 分子，能抑制人肝癌（HCC）细胞的侵袭和转移。在此，我们报告说，通过共显微注射两个编码 chHAb18 重链和轻链基因的盒，可在转基因小鼠的乳腺中高表达功能性 chHAb18。表达水平范围为 1.1-7.4mg ml(-1)，与转基因拷贝数无关。免疫分析表明 chHAb18 具有结合纯化抗原（即 HAb18G）或 HCC 细胞的能力和特异性。从转基因奶中提取的重组 chHAb18 表现出与 CHO 细胞衍生的 chHAb18 几乎相同的亲和力，为亲本鼠抗体 HAb18 的 68%。鉴于 HAb18 的成功临床应用，在转基因小鼠乳腺中表达的 chHAb18 是实现该抗体高产和规模化生产的重要一步。
