Cytokine Growth Factor Antibodies in Immunotherapy

A special issue of Antibodies (ISSN 2073-4468).

Deadline for manuscript submissions: closed (30 April 2013) | Viewed by 26854

Special Issue Editor


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Guest Editor
School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, NSW 2052, Australia
Interests: ADCC; neutralizing antibodies; cytokines; IL-21; IL-22; T cells, B cells; autoimmune disease; mucosal autoimmunity

Special Issue Information

Dear Colleagues,

In this issue, we aim to draw together some of the latest research on antibodies directed against cytokines used in both research and clinical settings. Cytokines are small cell-signaling protein molecules secreted by cells of the immune system that regulate host responses to infection, inflammation, and trauma. Cytokines deliver signals between cells, and often across short distances during cell-to-cell interactions, which influence cellular growth and differentiation.

Antibodies directed against cytokines have had an enormous impact on biomedical research. Research Laboratories, pharmaceutical and biotechnology industries continue to focus on the development of antibodies directed against cytokines for the treatment of cancer, chronic inflammation and autoimmune diseases. Attention has focused on blocking cytokines, which are harmful to the host and using antibodies bound to cytokines to expand subsets of T cells that can regulate immune responses. Strategies include neutralizing antibodies, cytokine-cytokine antibody complexes, soluble receptors, receptor antagonist and targeting molecules that are important for the processing of cytokines.

Dr. Cecile King
Guest Editor

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Keywords

  • cytokines
  • growth factors
  • anti-cytokine antibodies
  • immune complexes
  • autoimmunity
  • cancer
  • inflammation
  • cytokine receptor trap
  • potentiating antibodies
  • neutralizing antibodies
  • bioavailability

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Published Papers (2 papers)

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Research

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Article
Characterization of a Phospho-Specific Antibody to the Fcε Receptor γ Chain, Reveals Differences in the Regulation of Syk and Akt Phosphorylation
by Ryo Suzuki, Sarah Leach, Barbara Dema and Juan Rivera
Antibodies 2013, 2(2), 321-337; https://doi.org/10.3390/antib2020321 - 13 May 2013
Cited by 5 | Viewed by 8501
Abstract
We previously demonstrated that the Fc receptor γ-chain Y58(C-terminal tyrosine) is highly susceptible to dephosphorylation; a mechanism that controls the extent of Syk activation and the downstream signaling in mast cells. Here, we explored the importance of the γ-chain Y47 [...] Read more.
We previously demonstrated that the Fc receptor γ-chain Y58(C-terminal tyrosine) is highly susceptible to dephosphorylation; a mechanism that controls the extent of Syk activation and the downstream signaling in mast cells. Here, we explored the importance of the γ-chain Y47 (N-terminal tyrosine) in mast cell signaling. We generated a highly sensitive and versatile phospho-specific antibody that recognized the phosphorylated Y47 in various species. Using this antibody, we found that mutation of the FcεRIβ Y219 to phenylalanine caused a loss in the phosphorylation of the γ-chain Y47, consistent with the previously described role of Y219 in Lyn association with FcεRIβ and subsequent FcεRIγ phosphorylation. These conditions also diminished the tyrosine phosphorylation of Syk and LAT1 but, surprisingly, not the phosphorylation of Akt at T308. Mutation of Y47 or Y58 of the γ-chain also caused a marked inhibition of Syk and LAT1 phosphorylation, but only the latter mutant showed a reduction in Akt phosphorylation. These findings show that the full phosphorylation of Syk and LAT1 requires the FcεRIβ Y219 and both Y47 and Y58 of the γ-chain. However, T308 phosphorylation of Akt is largely independent of FcεRIγ Y47 phosphorylation and of the Lyn-binding site (Y219) on the FcεRIβ. Full article
(This article belongs to the Special Issue Cytokine Growth Factor Antibodies in Immunotherapy)
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Review

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Review
Molecular Engineering of Therapeutic Cytokines
by Rodrigo Vazquez-Lombardi, Brendan Roome and Daniel Christ
Antibodies 2013, 2(3), 426-451; https://doi.org/10.3390/antib2030426 - 3 Jul 2013
Cited by 44 | Viewed by 17816
Abstract
Over the past three decades, a large body of work has been directed at the development of therapeutic cytokines. Despite their central role in immune modulation, only a handful of cytokine therapeutics has achieved regulatory approval. One of the major challenges associated with [...] Read more.
Over the past three decades, a large body of work has been directed at the development of therapeutic cytokines. Despite their central role in immune modulation, only a handful of cytokine therapeutics has achieved regulatory approval. One of the major challenges associated with the therapeutic use of cytokines relates to their short serum half-life and low bioavailability. High doses are required to overcome these problems, which often result in dose-limiting toxicities. Consequently, most cytokines require protein engineering approaches to reduce toxicity and increase half-life. For this purpose, PEGylation, fusion proteins, antibody complexes and mutagenesis have been utilized. Here, we summarize past, recent and emerging strategies in this area. Full article
(This article belongs to the Special Issue Cytokine Growth Factor Antibodies in Immunotherapy)
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