| RRC ID |
44512
|
| Author |
Spiess C, Merchant M, Huang A, Zheng Z, Yang NY, Peng J, Ellerman D, Shatz W, Reilly D, Yansura DG, Scheer JM.
|
| Title |
Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies.
|
| Journal |
Nat Biotechnol
|
| Abstract |
By enabling the simultaneous engagement of two distinct targets, bispecific antibodies broaden the potential utility of antibody-based therapies. However, bispecific-antibody design and production remain challenging, owing to the need to incorporate two distinct heavy and light chain pairs while maintaining natural nonimmunogenic antibody architecture. Here we present a bispecific-antibody production strategy that relies on co-culture of two bacterial strains, each expressing a half-antibody. Using this approach, we produce 28 unique bispecific antibodies. A bispecific antibody against the receptor tyrosine kinases MET and EGFR binds both targets monovalently, inhibits their signaling, and suppresses MET and EGFR-driven cell and tumor growth. Our strategy allows rapid generation of bispecific antibodies from any two existing antibodies and yields milligram to gram quantities of bispecific antibodies sufficient for a wide range of discovery and preclinical applications.
|
| Volume |
31(8)
|
| Pages |
753-8
|
| Published |
2013-8-1
|
| DOI |
10.1038/nbt.2621
|
| PII |
nbt.2621
|
| PMID |
23831709
|
| MeSH |
Antibodies, Bispecific / biosynthesis*
Antibodies, Bispecific / immunology
Antibody Specificity
Bacteria / immunology
Bacteria / metabolism
Cell Line, Tumor
Coculture Techniques*
ErbB Receptors / genetics
ErbB Receptors / immunology*
Gene Expression Regulation, Bacterial / immunology
Humans
Immunoglobulin G / genetics
Immunoglobulin G / immunology
Neoplasms / immunology
Neoplasms / pathology
Neoplasms / therapy*
Protein Engineering
Proto-Oncogene Proteins c-met / genetics
Proto-Oncogene Proteins c-met / immunology*
|
| IF |
36.553
|
| Times Cited |
113
|
|
WOS Category
|
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
|
| Resource |
| Human and Animal Cells |
KP4(RCB1005) |
