Large Phage-Displayed Library Of Human Domain Antibodies (dAbs)
Background:
The National Cancer Institute's Nanobiology Program is seeking
statements of capability or interest from parties interested in
collaborative research to further develop, evaluate, or
commercialize a large phage-displayed human domain antibody (dAb)
library.
Technology:
Monoclonal antibody (mAb) is a class of specific, safe and
effective therapeutics against cancers and viral diseases. Phage
display is a powerful technology for construction of large
high-quality antibody libraries which have become vital sources for
selection of mAbs with high affinity and novel properties.
Previously, a large (15 billion clones) non-immune human antibody
phage display library was constructed from the lymph nodes, spleen
and peripheral blood lymphocytes of 50 donors. One antibody
isolated from this library included a stop codon in the light
chain, but was still selected as a functional heavy chain. The VH
domain of this antibody, designated m0, is highly soluble, stable,
monomeric and expressed at high levels in bacteria. M0 was used as
a framework to construct a large human antibody heavy chain
variable domain (dAb) library (25 billion clones) by grafting
naturally occurring complementarity-determining regions (CDRs) 2
and 3 of heavy chains from five human antibody Fab libraries and by
randomly mutating four putative solvent-accessible residues in CDR1
to A, D, S, or Y.
The antibodies from this library are small (about 14 kDa), highly
stable, and can be expressed at high levels as monomers. This
library could be a valuable source of antibodies targeting
size-restricted epitopes and antigens in obstructed locations where
efficient penetration could be critical for successful treatment.
Moreover, their small size allows for higher molar quantities per
gram of product, which should provide a significant increase in
potency per dose and a reduction in overall manufacturing cost.
Further R&D Needed:
- Continued selection of novel antibodies, primarily against
cancer-related antigens
R&D Status: Pre-clinical
development
IP Status: Research Tool. Patent
protection is not being pursued for this technology.
Value Proposition:
- Large human dAb library allows isolation of small antibodies
with such properties as high solubility, stability, high expression
levels (low cost for production), good penetration into solid
tumors, and low toxicity and rejection rates in vivo.
Contact Information:
John D. Hewes, Ph.D.
NCI Technology Transfer Center
Tel: 301-435-3121
Email: hewesj@mail.nih.gov
Please reference advertisement #731
Revision 10/01/2008