Comparing with
other display technologies, yeast display has build-in advantages: 1) As
eukaryotic, the antibody fragments displayed have proper folding and more amenable
for widely used CHO cell expression. 2)
With cutting edge cell sorting technology, the throughput of screening is order
of magnitude higher. 3) A quantification attribute could be introduced at early
round of selection.
Dingfu Biotarget Co., a tumor immunotherapy focused startup and majority owned subsidiary of Alphamab, has optimized the yeast display system and obtained a high quality naive fully human library. In short time, Dingfu Bio has fished out several fully human antibodies. One of that has been licensed out to a domestic pharmaceutical company for further development.
The yeast display library has been constructed from non-immunized healthy volunteers. With the diversity of 10E9, a few rounds of FACS sorting could generate binder with sub nano-molar affinity. In addition, error prone PCR could be easily applied to the lead or focused library for affinity maturation although not usually necessary.
With
the powerful platform, multiple leads could be fished out within 8-10 weeks,
and another 4-6 weeks for affinity maturation to pM if necessary. At the same
time, a fine tuned selection scheme had been developed towards antibody agonist.
We have obtained fully human antibodies with strong agonize activity towards several
targets belong to TNF receptor family.
Finally, with yeast display, focused dAb libraries have been constructed for humanization and affinity maturation.
