학술논문

Mining Naïve Rabbit Antibody Repertoires by Phage Display for Monoclonal Antibodies of Therapeutic Utility.
Document Type
Article
Source
Journal of Molecular Biology. Sep2017, Vol. 429 Issue 19, p2954-2973. 20p.
Subject
*THERAPEUTIC use of monoclonal antibodies
*IMMUNIZATION
*CHIMERIC antigen receptors
*NUCLEOTIDE sequence
*LABORATORY rabbits
Language
ISSN
0022-2836
Abstract
Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but, in some cases, also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large naïve rabbit antibody repertoire represented by a phage display library encompassing > 10 billion independent antibodies in chimeric rabbit/human Fab format and validated it by next-generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity. Moreover, ROR1- and ROR2-targeting rabbit mAbs demonstrated therapeutic utility as components of chimeric antigen receptor-engineered T cells, further corroborating the value of the naïve rabbit antibody library as a rich and virtually unlimited source of rabbit mAbs. [ABSTRACT FROM AUTHOR]