PMID: 2115168Jul 1, 1990Paper

Expression and characterization of an antibody binding specificity joined to insulin-like growth factor 1: potential applications for cellular targeting

Proceedings of the National Academy of Sciences of the United States of America
S U Shin, S L Morrison

Abstract

To create antibody molecules with improved functional properties, a growth factor (insulin-like growth factor 1, IGF1) was used to replace the constant region of a chimeric mouse-human IgG3 anti-dansyl antibody. The chimeric heavy chain was expressed with an anti-dansyl-specific chimeric kappa light chain. The IgG3-IGF1 chimeric protein retained its specificity for the antigen dansyl. The chimeric proteins bound to the IGF1 receptors of the human lymphoblast IM-9, albeit with reduced affinity, and elicited some of the same biologic effects (increased glucose and amino acid uptake) in human KB cells as did human IGF1, but with reduced specific activity. The reduced affinity and biologic activity may result from several things: the presence of the unprocessed IGF1 moiety, the large size of the IgG3-IGF1 chimeric protein (160 kDa) compared with IGF1 (7 kDa), and three amino acid substitutions in rat IGF1 compared with human IGF1, which may lead to decreased affinity for the human IGF1 receptor. The chimeric proteins show that it is feasible to produce a new family of immunotherapeutic molecules targeted to growth factor receptors.

References

Jun 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·A F LoBuglioM B Khazaeli
Jun 1, 1985·Journal of Neurochemistry·W M PardridgeJ Yang
Dec 1, 1986·The Journal of Clinical Endocrinology and Metabolism·P MisraR G Rosenfeld
May 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·A Y LiuI Hellström
Jan 1, 1987·Journal of Neuroscience Research·J B FishmanR E Fine
Dec 13, 1984·Nature·G L BoulianneM J Shulman
Nov 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·S L MorrisonV T Oi
Oct 1, 1982·The Journal of Experimental Medicine·D E Yelton, M D Scharff
Nov 1, 1981·The Journal of Experimental Medicine·D J ZackM D Scharff

❮ Previous
Next ❯

Citations

Jan 1, 1994·Archives of Virology·J B Lyczak, S L Morrison
Sep 1, 1991·Molecular Immunology·H R HoogenboomJ C Raus
Apr 1, 1991·Current Opinion in Immunology·A C Hiatt
Apr 27, 1992·Journal of Immunological Methods·M R WalkerA M Roberts
Mar 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·S U ShinS L Morrison
Apr 1, 1995·The Journal of Cell Biology·W J LaRochelleS A Aaronson
Jul 1, 1992·Pharmacology & Toxicology·W M Pardridge
Jan 12, 1999·The Journal of Clinical Investigation·H F ZhangS Tomlinson
Feb 1, 2009·Expert Opinion on Drug Discovery·Chien-Hsing ChangDavid M Goldenberg
Jan 1, 1993·International Reviews of Immunology·S U ShinS L Morrison
Apr 1, 1992·Bio/technology·H UedaH Nishimura
Dec 1, 1992·Immunological Reviews·J R Adair
Feb 16, 1996·The Journal of Biological Chemistry·J B LyczakS L Morrison
May 16, 2001·The Journal of Biological Chemistry·H ZhangS Tomlinson

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antibody Specificity

Antibodies produced by B cells are highly specific for antigen as a result of random gene recombination and somatic hypermutation and affinity maturation. As the main effector of the humoral immune system, antibodies can neutralize foreign cells. Find the latest research on antibody specificity here.