• Research Reagents >

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

• 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.