Sep 20 (Reuters Health) - Scientists from the University of Illinois have developed monovalent antibody fragments with ligand binding affinities more than 1000-fold higher than the highest antigen-binding affinities ever achieved with an engineered protein.
"Generation of antibodies that bind essentially irreversibly relative to the relevant physiological time scale could improve efficacy for cancer immunotherapy with noninternalizing tumor-associated antigens and passive immunization against viral and microbial pathogens," Dr. Eric T. Boder and colleagues, from Urbana, Illinois, say in the September 12th online issue of the Proceedings of the National Academy of Sciences.
The investigators used affinity mutagenesis and screening to generate mutants of yeast surface-displayed antibodies. After four cycles of mutagenesis, they developed antibody mutants with slower dissociation constants than those for the streptavidin-biotin complex, which "is near the affinity ceiling of the tertiary immune response."
In a related commentary, Dr. Jefferson Foote, of the University of Washington, Seattle, and Dr. Herman N. Eisen, of the Massachusetts Institute of Technology, in Cambridge, speculate that while the proposed "molecular ceiling" for antigen-antibody affinity may not exist, Dr. Boder and colleagues have likely neared the "methodological ceiling" for this activity.
Online Proc Natl Acad Sci USA Early Edition. September 12, 2000;doc 2972. |
