Frontier of therapeutic antibody discovery: The challenges and how to face them

Table 1 Comparison of major technology platforms for therapeutic antibody discovery

Platforms	Main applications	Major advantages	Key disadvantages	FDA approved therapeutic antibodies
Hybridoma	Generate hits and research reagents	Mature technology and cost effective	Potential immunogenicity	Orthoclone, Zevalin, Bexxar
Humanization	Generate therapeutic candidates	Well established and low cost	Not fully human antibodies	ReoPro, Rituxan, Simulect, Remicade, Erbitux, Adcetris, Zenapax, Synagis, Herceptin, Mylotarg, Mabcampath, Xolair, Actemra, Avastin, Tysabri, Lucentis, Soliris, Cimzia, Perjeta
Phage display	Generate hits and therapeutic candidates	Large library size (> 10E10) and robust screening; fully human antibodies	Not all antibodies express well in Escherichia coli and require engineering	Humira and Benlysta
Yeast display	Improve affinity and stability	Eukaryotic host; targeted sorting by FACS	Relatively small library size	None
Transgenic Rodents	Generate therapeutic candidates	High affinity fully human antibodies	Technology accessibility	Vectibis, Ilaris, Simponi, Stelara, Arzerra, Prolia, Yervoy

FDA: Food and Drug Administration; FACS: Fluorescence activated cell sorting.