Expression and characterization of an antibody binding specificity joined to insulin-like growth factor 1

Potential applications for cellular targeting

Seung-Uon Shin, Sherie L. Morrison

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

To create antibody molecules with improved functional properties, a growth factor (insulin-like growth factor 1, 1GF1) 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 κ 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-IGFl 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.

Original languageEnglish
Pages (from-to)5322-5326
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number14
StatePublished - Dec 1 1990
Externally publishedYes

Fingerprint

Antibody Specificity
Somatomedins
Immunoglobulin G
Proteins
KB Cells
Growth Factor Receptors
Amino Acid Substitution
Anti-Idiotypic Antibodies
Intercellular Signaling Peptides and Proteins
Light
Antigens
Amino Acids
Glucose
Antibodies

Keywords

  • Chimeric antibody
  • Fusion protein
  • Growth factor receptors
  • Immunotherapy

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

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