In Vivo Properties of an IgG3-IL-2 Fusion Protein: A General Strategy for Immune Potentiation 1

Eric T. Harvill, Jennifer M. Fleming, Sherie L. Morrison

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

In this report, we describe a strategy for enhancing the immunogenicity of a wide variety of Ags by linking them to IL-2 via an IgG3-IL-2 fusion protein with high affinity for a convenient hapten Ag, dansyl (DNS; N,N-dimethyl-1-aminonaphthalene-5-sulfonyl chloride). This fusion protein, anti-DNS-IgC3-IL-2, combines the functional characteristics of its constituents and has pharmacokinetic properties that are greatly improved over those of IL-2 and a previously described IgG1-IL-2 fusion. The molecule is intact and recoverable from the blood of mice hours after i.p. injection and reaches distant organs throughout the animal. The 7-h in vivo half-life of this molecule is much longer than that of IL-2, addressing a major obstacle in the application of IL-2 to human diseases, including cancer and AIDS. Additionally, the Ab's specificity for the hapten dansyl and the convenient chemistry of dansyl provide a means to link IL-2 to virtually any molecule of interest without the complexities and uncertainties of making IL-2 fusions with each molecule individually. Using hapten-conjugated-BSA (DNS-BSA) as a model Ag we show that the Ab response elicited by anti-DNS-IgG3-IL-2-bound DNS-BSA-Sepharose injected into mice is increased over that of DNS-BSA-Sepharose or anti-DNS-IgG3-bound DNS-BSA-Sepharose. Anti-DNS-IgG3-IL-2 also increased the Ab response to soluble DNS-BSA after a booster injection. This system should be useful in testing the ability of IL-2 to potentiate the immune response to Ag and in screening a large number of potential Ags for use in vaccines. The dramatically improved pharmacokinetics should also overcome one of the major difficulties in applying IL-2 to the treatment of human disease, its short half-life.

Original languageEnglish (US)
Pages (from-to)3165-3170
Number of pages6
JournalJournal of Immunology
Volume157
Issue number7
StatePublished - Oct 1 1996

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Staphylococcal Protein A
Interleukin-2
Immunoglobulin G
Haptens
Sepharose
Half-Life
Pharmacokinetics
1-Naphthylamine
Animal Structures
Injections
Uncertainty
Acquired Immunodeficiency Syndrome
Proteins
Vaccines

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Harvill, E. T., Fleming, J. M., & Morrison, S. L. (1996). In Vivo Properties of an IgG3-IL-2 Fusion Protein: A General Strategy for Immune Potentiation 1. Journal of Immunology, 157(7), 3165-3170.
Harvill, Eric T. ; Fleming, Jennifer M. ; Morrison, Sherie L. / In Vivo Properties of an IgG3-IL-2 Fusion Protein : A General Strategy for Immune Potentiation 1. In: Journal of Immunology. 1996 ; Vol. 157, No. 7. pp. 3165-3170.
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Harvill, ET, Fleming, JM & Morrison, SL 1996, 'In Vivo Properties of an IgG3-IL-2 Fusion Protein: A General Strategy for Immune Potentiation 1', Journal of Immunology, vol. 157, no. 7, pp. 3165-3170.

In Vivo Properties of an IgG3-IL-2 Fusion Protein : A General Strategy for Immune Potentiation 1. / Harvill, Eric T.; Fleming, Jennifer M.; Morrison, Sherie L.

In: Journal of Immunology, Vol. 157, No. 7, 01.10.1996, p. 3165-3170.

Research output: Contribution to journalArticle

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T1 - In Vivo Properties of an IgG3-IL-2 Fusion Protein

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AU - Harvill, Eric T.

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