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Cloning and characterization of novel tumor-targeting immunocytokines based on murine IL7

Paper ID Volume ID Publish Year Pages File Format Full-Text
23769 43471 2011 9 PDF Available
Title
Cloning and characterization of novel tumor-targeting immunocytokines based on murine IL7
Abstract

We generated and characterized novel antibody–cytokine fusion proteins (“immunocytokines”) based on murine interleukin-7 (IL7), an immunomodulatory protein which has previously shown anti-cancer activity in preclinical models and whose human counterpart is currently being investigated in clinical trials. The sequential fusion of the clinical-stage antibody fragment scFv(F8), specific to a tumor-associated splice isoform of fibronectin, yielded an immunocytokine (termed “F8-mIL7”) of insufficient pharmaceutical quality and in vivo tumor targeting performance, with a striking dose dependence on tumor targeting selectivity. By contrast, a novel immunocytokine design (termed “F8-mIL7-F8”), in which two scFv moieties were fused at the N- and C-terminus of murine IL7, yielded a protein of excellent pharmaceutical quality and with improved tumor-targeting performance [tumor: blood ratio = 16:1, 24 h after injection]. Both F8-mIL7 and F8-mIL7-F8 could induce tumor growth retardation in immunocompetent mice, but were not able to eradicate F9 tumors. The combination of F8-mIL7-F8 with paclitaxel led to improved therapeutic results, which were significantly better compared to those obtained with saline treatment. The study indicates how the engineering of novel immunocytokine formats may help generate fusion proteins of acceptable pharmaceutical quality, for those immunomodulatory proteins which do not lend themselves to a direct fusion with antibody fragments.

Keywords
IL2, Interleukin 2; IL10, Interleukin 10; IL12, Interleukin 12; IL15, Interleukin 15; GM-CSF, granulocyte macrophage colony stimulating factor; IFNα, Interferon alpha; IFNγ, Interferon gamma; TNF, tumor necrosis factor; IL7, interleukin 7; hIL7, human int
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Cloning and characterization of novel tumor-targeting immunocytokines based on murine IL7
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 154, Issue 1, 10 June 2011, Pages 84–92
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us