Innovation and Development

A Novel Approach to Produce Human Monoclonal Antibody

Therapeutic human monoclonal antibody has grown into multi-billion industry. Thus developing reliable culture conditions for the large scale human monoclonal antibody production are practically important. Since it was introduced in late 1990s Wave bioreactor has been used for protein production by mammalian and insect cells. However, using Wave bioreactor to produce human monoclonal antibody by stable Drosophila Schneider 2 (S2) cell transfectants has not been reported before. In this study, research associate Wang Lulan and Ph.D. student Hu Hongxing in Prof. Paul Zhou’s laboratory at Institut Pasteur of Shanghai, CAS, in collaboration with Dr. Yang Jianjun at the Fast Trak Center, GE (China) Research and Development Center, so-transfected S2 cells with an inducible vector expressing human monoclonal antibody heavy and light chains, respectively, specific for influenza hemagglutinin. Stable S2 transfectant clone that produce the highest amount of human monoclonal antibody was selected by limiting dilution assay and inoculated into two 2-L disposable cellbags, where cell growth and antibody production were compared between batch and perfusion cultures using Wave bioreactor. The data show perfusion culture can get higher antibody yield. The antibody produced by both cultures displays full neutralizing activity. These results strongly support for using Wave bioreactor in perfusion culture for a large scale production of human monoclonal antibody by stable S2 cell transfectants. On Dec. 25, 2011, the result was published online on Molecular Biotechnology. This is the first report on using Wave bioreactor to produce human monoclonal antibody by stably transfected Drosophila S2 cells.

Systematic Research of Cytotoxicity of Cadmium-based Quantum Dots

Recently Huang and Fan groups in Shanghai Institute of Applied Physics (SINAP), CAS were invited to publish a leading opinion paper (The cytotoxicity of cadmium-based quantum dots) on Biomaterials (2012, 33, 1238-1244). In this article, they reported their latest results in a systematic study of the cytotoxicity of cadmium-based QDs (quantum dots) and aimed to summarize recent progress on mechanistic studies on this topic. They compared the cytotoxicity of three kinds of QDs with different structures, and found out that unprotected CdTe QDs are much more toxic than QDs with core-shell structures, suggesting that released cadmium ions are responsible for the cytotoxicity of cadmium-based QDs (Biomaterials, 2009, 30, 19-25). Further study indicated that the CdTe QDs-induced cellular toxicity is much higher than equal concentration of free cadmium ions. Therefore the heavy metal toxic effect of cadmium ions is not the only contributor of the cytotoxicity of CdTe QDs. Other factors, such as size effect and surface effect of nano-materials also contributed to the toxicity of QDs (Biomaterials, 2010, 31, 4829-4834). Subsequently, researchers compared changes of genome-wide gene expression induced by CdTe QDs and CdCl2, which showed obvious similarities. Researchers also utilized synchrotron-based soft transmission X-ray microscopy (STXM) and transmission electron microscopy (TEM) to trace the subcellular localization of CdTe QDs, and found that the QDs significantly enriched around the nucleus. Such intracellular distribution pattern of QDs caused a significant nano-effect. In addition, the cadmium ions on the surface of CdTe QDs may cause cytotoxicity through contacting with the nucleus directly (Biomaterials 2012, 33, 1238-1244).Based on existing results, it was proposed that the cytotoxicity of cadmium-based QDs are majorly caused by cadmium ions dissociated from the surface of the QDs, and impacted greatly by the intracellular distribution of QDs. This study provided a new mechanism on the systematic understanding of the biocompatible issues of QDs, and expected to play a guiding role for the application of QDs in biological imaging, medical diagnosis and treatment.