Recombinant Interleukin-12 for Immunotherapy: A Double-Sided Sword

Author(s): A. Hombach , C. Heuser , A. Stallmach , H. Abken .

Journal Name: Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents

Volume 5 , Issue 3 , 2005

Abstract:

The innate and adaptive immune responses are closely linked and mutually reinforcing. The type of adaptive immune response is strongly influenced by the cytokines produced by innate immune cells. Interleukin-12 (IL-12) plays a key role in linking innate immunity to an adaptive T helper-1 (Th1) response against pathogens and tumor cells, thereby counteracting an imbalanced Th2 immune response. These properties make IL-12 a powerfull candidate to revert the Th2 dominance into a polarized immune response, e.g., in the tumor environment. Due to the heterodimeric structure, recombinant IL-12 fusion proteins provide the potential to create agonistic as well as antagonistic derivatives. The latter IL-12 derivatives block IL-12 activity by competitive binding to the receptor, e.g., to repress chronic inflammatory processes. Here we discuss functional properties of recombinant IL-12 constructs for use in immunotherapy, particularly (i) the agonistically acting IL-12(p40-p35) protein designed to boost anti-tumor immunity by reverting Th2 dominance and by increasing the effector functions of tumor infiltrating T- and NK-cells, and (ii) the antagonistically acting IL-12(p40)2 dimer protein designed to block IL-12 functions in chronic inflammatory diseases. Despite their limitations, both types of recombinant IL-12 derivatives have significant implications for the immunotherapy of malignant diseases as well as of bowel disease.

Keywords: recombinant il, immunocytokine, immunotherapy, chronic inflammatory diseases, nk-cell, t-cell

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Article Details

VOLUME: 5
ISSUE: 3
Year: 2005
Page: [269 - 276]
Pages: 8
DOI: 10.2174/1568013054022472
Price: $58

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