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Semin Oncol. 2014 Oct;41(5):623-36. doi: 10.1053/j.seminoncol.2014.08.002. Epub 2014 Aug 12.

Antibody-cytokine fusion proteins for treatment of cancer: engineering cytokines for improved efficacy and safety.

Author information

1
Division of Hematology & Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA.
2
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA.
3
Division of Hematology & Oncology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA. Electronic address: jtimmerman@mednet.ucla.edu.

Abstract

The true potential of cytokine therapies in cancer treatment is limited by the inability to deliver optimal concentrations into tumor sites due to dose-limiting systemic toxicities. To maximize the efficacy of cytokine therapy, recombinant antibody-cytokine fusion proteins have been constructed by a number of groups to harness the tumor-targeting ability of monoclonal antibodies. The aim is to guide cytokines specifically to tumor sites where they might stimulate more optimal anti-tumor immune responses while avoiding the systemic toxicities of free cytokine therapy. Antibody-cytokine fusion proteins containing interleukin (IL)-2, IL-12, IL-21, tumor necrosis factor (TNF)α, and interferons (IFNs) α, β, and γ have been constructed and have shown anti-tumor activity in preclinical and early-phase clinical studies. Future priorities for development of this technology include optimization of tumor targeting, bioactivity of the fused cytokine, and choice of appropriate agents for combination therapies. This review is intended to serve as a framework for engineering an ideal antibody-cytokine fusion protein, focusing on previously developed constructs and their clinical trial results.

PMID:
25440607
PMCID:
PMC4354941
DOI:
10.1053/j.seminoncol.2014.08.002
[Indexed for MEDLINE]
Free PMC Article

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