Lab research for the development of human anti-diphtheria Mabs in CHO cells

Monoclonal anitbodies (Mab) have been used successfully for treating human diseases. However, conventional Mabs are derived from mouse. Injection of murine Mabs into humans will cause adverse effects. The development of human Mabs against diphtheria could offer a commercially viable alternative to equine antitoxin for treating human diphtheria with a number of potential advantages including higher potency per unti dose, a greater margin of safety, and a sustainable supply. The current SBIR applicaiton proposes to produce a prototype human Mab as diphtheria antitoxin, with a path to IND or licensure. This anti-DT Mab will be selected from a human antibody phage display library, and will be manufactured in the industry preferred, FDA-approved workhorse, Chinese hamster overy (CHO cells. in Phase I, proof-of-concept will be established to produce such anti-DT Mab in stable CHO cell lines at laboratory levels. Both wildtype and Fut8-/- CHO cells will be used, and we will determine if defucosylated anti-DT Mab from Fut8-/- CHO cells exhibits higher potency in neutralizing diphtheria toxin in vero cell assays. By selecting high producers of stable CHO cell lines, our goal is to provide an uninterrupted supply of specific diphtheria antitoxin available for patient management, both in industrialized and developing countries.