Functional properties of antibody insulin-like growth factor fusion proteins

Seung-Uon Shin, Philip Friden, Marjorie Moran, Sherie L. Morrison

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Genetic engineering and expression techniques have been used to produce antibody growth factor fusion proteins. Insulin-like growth factors (IGFs) 1 and 2 have been fused to mouse-human chimeric IgG3 at the end of C(H)1, immediately after the hinge, and at the end of C(H)3. Fusion heavy chains of the expected molecular weight were expressed, assembled with a co-expressed light chain, and secreted. The resulting molecules continued to bind antigen; they also bound the growth factor receptors, albeit with decreased affinity. The molecule with IGF1 attached after C(H)3 (C(H)3-IGF1) had reduced ability to carry out complement-mediated cytolysis. In contrast the molecule with IGF2 attached after C(H)3 (C(H)3-IGF2) showed an approximately 50-fold increase in its ability to effect complement-mediated cytolysis and so should be an effective cytolytic agent. Both C(H)3-IGF1 and C(H)3-IGF2 bound FcγRI with affinity similar to that of IgG3. The growth factor fusion proteins showed small but significant uptake into the brain parenchyma.

Original languageEnglish
Pages (from-to)4979-4985
Number of pages7
JournalJournal of Biological Chemistry
Volume269
Issue number7
StatePublished - Feb 18 1994
Externally publishedYes

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Somatomedins
Antibodies
Intercellular Signaling Peptides and Proteins
Fusion reactions
Immunoglobulin G
Molecules
Genetic Engineering
Growth Factor Receptors
Genetic engineering
Proteins
Molecular Weight
Hinges
Light
Antigens
Brain
Molecular weight

ASJC Scopus subject areas

  • Biochemistry

Cite this

Functional properties of antibody insulin-like growth factor fusion proteins. / Shin, Seung-Uon; Friden, Philip; Moran, Marjorie; Morrison, Sherie L.

In: Journal of Biological Chemistry, Vol. 269, No. 7, 18.02.1994, p. 4979-4985.

Research output: Contribution to journalArticle

Shin, S-U, Friden, P, Moran, M & Morrison, SL 1994, 'Functional properties of antibody insulin-like growth factor fusion proteins', Journal of Biological Chemistry, vol. 269, no. 7, pp. 4979-4985.
Shin, Seung-Uon ; Friden, Philip ; Moran, Marjorie ; Morrison, Sherie L. / Functional properties of antibody insulin-like growth factor fusion proteins. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 7. pp. 4979-4985.
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