Selective Activation of Intracellular Signalling Pathways in Dendritic Cells for Cancer Immunotherapy

Author(s): Frederick Arce, Grazyna Kochan, Karine Breckpot, Holly Stephenson, David Escors

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 12 , Issue 1 , 2012

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One of the major challenges in achieving effective anti-cancer immunotherapy is to counteract immunological tolerance. Most tumor-associated antigens (TAAs) are sensed as self. Hence, naturally occurring tolerance towards them has to be overcome. Fortunately, there is increasing evidence that anti-tumor immune responses occur and play a crucial role in the success of well-established anti-neoplastic therapies such as radiotherapy and chemotherapy. In fact, their effectiveness relies on signalling by pattern recognition receptors such as Toll-like receptors (TLRs). TLR signal transduction involves activation of a few well-known pathways, of which nuclear factor κB (NF-κB) and mitogen activated protein kinases (MAPKs) are possibly the best characterized. Therefore, constitutive activation of these pathways in immune cells can potentially enhance anti-tumor immunity, especially when targeted to professional antigen presenting cells (APCs) such as dendritic cells (DCs). Several strategies have been devised to test this hypothesis, including constitutive activation of TLRs, NF-κB and MAPKs (extracellular-signal regulated kinase (ERK), p38 and c-Jun kinase 1 (JNK1)). Activation of these pathways in mouse and human DCs has differential effects in immunogenicity and in many cases, enhanced antitumor immunity in pre-clinical models, establishing the basis for future clinical applications.

Keywords: Cancer, Cytokine, Dendritic cells, Immunotherapy, Lentivector, Signalling, Tolerance, TLR, Tumor, Biosafety

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Article Details

Year: 2012
Page: [29 - 39]
Pages: 11
DOI: 10.2174/187152012798764679

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