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Therapeutic Antibodies

Date:2016/9/6 Views:495

  1. Mission

Our aim is to construct a technological platform for the development of innovative therapeutic antibodies. After high throughput screening, those innovative antibodies with therapeutic potential will be engineered and assessed for druggability to obtain the clinical candidate leaders, which can be applied to a broad range of translational and preclinical studies. 

  1. Platform

We have extensive experience in antibody screening & verification. In addition to mice, rats, monkeys and human antibody screening system, we have diversities of disease cell and animal models, Specific pathogen-free (SPF) laboratory, and Opera Phenix High Content Screening System, flow cytometry, laboratory automation workstation, high-performance liquid chromatography (HPLC) and other analysis equipment. Simultaneously, a variety of pathogens and tumor antibody libraries has been established for screening innovative candidate therapeutic antibodies.

We has phage-based display library technology for antibody humanization and affinity maturation. High-yield transient expression technology and CRISPR/Cas9 gene editing system are built for various macro-molecules transient epression and stable cell lines construction in CHO and HEK293. In-house serum-free medium has been used for bench-scale recombinant protein production. Novel drug evaluation system contains the product quality, preparation, accelerated stability assessment, half-life assessment in non-human primates and other assessment techniques.

  1. Innovative antibodies with therapeutic potential

Many novel candidate antibodies have been screened out against HBV, RSV, highly pathogenic avian influenza virus, PD-1/L1 and EV71. Showing highly neutralization activities in intro and therapeutic efficacy in animal models, some innovative antibodies have the potency to be developed as antibody drug candidates.

Chronic hepatitis B infection is a global public health problem. The approved anti-HBV drugs, which are either interferon or nucleus(t)ide analogs, can only induce disease remission, but not effectively eradicate the virus. The ideal endpoint for anti-HBV therapy is the loss of hepatitis B surface antigen (HBsAg); however, treatment options based on current drugs rarely result in HBsAg clearance. It is urgent to develop novel drugs to clear HBsAg or inhibit HBsAg level potently. Over 500 monoclonal antibodies were evaluated in HBV transgenic mice in our lab, and significant decreases of HBsAg in serum and hepatocyte were observed in mice that received mAbs that recognized unique epitope (Gut, 2015). At present, we have completed the humanization and drugability evaluation, American Pharmaceutical Companies show great interests in further development of the antibody as a drug.

Respiratory syncytial virus (RSV) therapeutic antibody. RSV is the third largest cause of children death due to lower respiratory tract infection, almost all children before 2 years old have ever infected with RSV, and more than 10% of the children with the disease need to be hospitalized which lead to high health burden. As so far, the specific treatment to RSV is still unavailable. Cooperateing with the US National Institutes of Health (NIH) Vaccine Center, we co-discovered the structure of the new epitope of the RSV surface membrane fusion protein (Science, 2013) as well as a functional epitope (patent application No. 201310082338.1). It has been shown that the in vitro neutralizing activity of monoclonal antibody (eg. 5C4) directing to the epitope was about 100 times higher than that of the antibody drug Synagis. So it could be developed as a potential anti-RSV treatment.

For the research on therapeutic antibodies to highly pathogenic avian influenza virus, we have discovered several broadly reactive antibodies directly against the receptor-binding site of the hemagglutinin which can neutralize diverse clades of H5N1 influenza virus isolates since 1996. These antibodies should provide a novel promising alternative for the treatment of H5N1 infection. This study has acquired the venture capital investment by the Kleiner Perkins Caufield & Byers Company (KPCB) in the United States; For the research on therapeutic antibodies in seasonal influenza virus, we have isolated a broadly- neutralizing antibody which can neutralize a broad spectrum of seasonal H1N1 viruses since 1918 and the 2009 pandemic H1N1 virus. Because of its potential value, we have signed a contract on continuous research of this antibody between our institute and Sanofi Pasteur Biologics, LLC.

In recent years, cancer immunotherapy has achieved great success. PD-1 monoclonal antibody targeting drugs has rapidly become a global hot spot. We have screened out two murine monoclonal antibody functionally equivalent to commercial antibodies. The high-blocking activity of humanized antibodies could be developed into promising anti-tumor antibody drugs.

EV71 is the major pathogen of hand, foot and mouth disease (HFMD) associated with severe cases and deaths of children. However, there is no prophylactic vaccines or therapeutic drugs available thus far. We constructed an EV71-specific virus strains library containing 6 genotypes, and also developed an efficient neutralization test based on the enzyme-linked immunoblot (Nt-ELISPOT) assay (Plos ONE, 2013; CVI, 2014). In addition, we constructed the EV71-specific monoclonal antibody library containing 400 clones, followed by the establishment of anti-EV71 neutralizing mAb panel including 78 clones (Vaccine, 2013). Some antibodies with treatment potential to EV71 infection will provide important candidates for the development of therapeutic drugs of EV71 (Theranostics, 2014; Plos ONE, 2014).

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