Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 429, Issue 19, Pages 2954-2973Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2017.08.003
Keywords
antibody engineering; ROR1; ROR2; chimeric antigen receptors; cancer therapy
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Funding
- National Institutes of Health grants [U01 CA174844, R01 CA181258]
- Lymphoma Research Foundation
- Klorfine Foundation
- Holm Charitable Trust
- NBE-Therapeutics
- NATIONAL CANCER INSTITUTE [U01CA174844, R01CA204484, R01CA181258] Funding Source: NIH RePORTER
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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 nave 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 na ve rabbit antibody library as a rich and virtually unlimited source of rabbit mAbs. (C) 2017 Elsevier Ltd. All rights reserved.
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