THERAPEUTIC ANTIBODIES

Human Theurapeutic Antibodies and Apollo hcx Proteins: A Golden Opportunity

Biologic agents, specifically monoclonal humanized antibodies, are fast becoming the focus of the pharmaceutical industry. They have lower immunogenicity, have longer half-lives and prolonged biologic effects, require less frequent administration and have minimal toxicity. Monoclonal antibodies are FDA approved for diseases such as cancer [Adams and Weiner (2005) Nat Biotechnol. 23:1147-1157], psoriasis and rheumatoid arthritis [Saripalli and Gaspari (2005) J Drugs Dermatol. 4:233-245.) and multiple sclerosis [Sheremata et al. (2005) CNS Drugs 19:909-922].

Ideally the best antigens to use in the immunization step during the development of human therapeutic antibodies would be human proteins expressed from human cells containing human specific glycosylation.

Glycosylation patterns are species specific, as such human recombinant protein from other mammalian cells such as mouse or hamster contain dissimilar glycan patterns. Human proteins produced from E. coli do not have any glycosylation. Therefore, antibodies generated against human proteins derived from other sources apart from human cells may have altered affinities to the target protein. These antibodies may recognise an epitope that is partially masked by a bulky glycan structure.

This hypothesis is supported by our observation that an antibody-based detection system (ELISA) for IL-3 exhibited different specificities for IL-3 produced from bacteria, insect and human (Apollo hcx) cells (Fig.1). The antibody from this ELISA assay was raised against bacterially expressed IL-3, and it had the highest affinity for IL-3 produced from bacterial cells. These results highlight the importance of using proteins with human specific glycosylation for therapeutic antibody development.

Apollo's increasing number of commercially available human glycosylated proteins will hopefully usher in a new era of biologic therapeutics.

View Apollo's hcx™ product range:

• » Recombinant Human Proteins
• » ELISA Kits