IgE-based Immunotherapy of Cancer -A Comparative Oncology Approach

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Abstract

Antibody-based immunotherapies are important therapy options in human oncology. Although human humoral specific immunity is constituted of five different immunoglobulin classes, currently only IgG-based immunotherapies have proceeded to clinical application.

This review, however, discusses the benefits and difficulties of IgE-based immunotherapy of cancer, with special emphasis on how to translate promising preclinical results into clinical studies. Pursuing the “Comparative Oncology” approach, novel drug candidates are investigated in clinical trials with veterinary cancer patients, most often dogs. By this strategy drug development could be speeded up, animal experiments could be reduced and novel therapy options could be introduced benefitting humans as well as man’s best friend.

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Most cited references 142

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Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses.

Pierre Bruhns, Bruno Iannascoli, Patrick England … (2009)

Distinct genes encode 6 human receptors for IgG (hFcgammaRs), 3 of which have 2 or 3 polymorphic variants. The specificity and affinity of individual hFcgammaRs for the 4 human IgG subclasses is unknown. This information is critical for antibody-based immunotherapy which has been increasingly used in the clinics. We investigated the binding of polyclonal and monoclonal IgG1, IgG2, IgG3, and IgG4 to FcgammaRI; FcgammaRIIA, IIB, and IIC; FcgammaRIIIA and IIIB; and all known polymorphic variants. Wild-type and low-fucosylated IgG1 anti-CD20 and anti-RhD mAbs were also examined. We found that (1) IgG1 and IgG3 bind to all hFcgammaRs; (2) IgG2 bind not only to FcgammaRIIA(H131), but also, with a lower affinity, to FcgammaRIIA(R131) and FcgammaRIIIA(V158); (3) IgG4 bind to FcgammaRI, FcgammaRIIA, IIB and IIC and FcgammaRIIIA(V158); and (4) the inhibitory receptor FcgammaRIIB has a lower affinity for IgG1, IgG2, and IgG3 than all other hFcgammaRs. We also identified parameters that determine the specificity and affinity of hFcgammaRs for IgG subclasses. These results document how hFcgammaR specificity and affinity may account for the biological activities of antibodies. They therefore highlight the role of specific hFcgammaRs in the therapeutic and pathogenic effects of antibodies in disease.

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Fcgamma receptors: old friends and new family members.

Falk Nimmerjahn, Jeffrey V. Ravetch (2006)

Although cellular receptors for immunoglobulins were first identified nearly 40 years ago, their central role in the immune response was discovered only in the last decade. They are key players in both the afferent and efferent phase of an immune response, setting thresholds for B cell activation, regulating the maturation of dendritic cells, and coupling the exquisite specificity of the antibody response to innate effector pathways, such as phagocytosis, antibody-dependent cellular cytotoxicity, and the recruitment and activation of inflammatory cells. Moreover, because of their general presence as receptor pairs consisting of activating and inhibitory molecules on the same cell, they have become a paradigm for studying the balance of positive and negative signals that ultimately determine the outcome of an immune response. This review will summarize recent results in Fc-receptor biology with an emphasis on data obtained in in vivo model systems.

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Feedback regulation of EGFR signalling: decision making by early and delayed loops.

Roi Avraham, Yosef Yarden (2011)

Human-made information relay systems invariably incorporate central regulatory components, which are mirrored in biological systems by dense feedback and feedforward loops. This type of system control is exemplified by positive and negative feedback loops (for example, receptor endocytosis and dephosphorylation) that enable growth factors and receptor Tyr kinases of the epidermal growth factor receptor (EGFR)/ERBB family to regulate cellular function. Recent studies show that the collection of feedback regulatory loops can perform computational tasks - such as decoding ligand specificity, transforming graded input signals into a digital output and regulating response kinetics. Aberrant signal processing and feedback regulation can lead to defects associated with pathologies such as cancer.

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Author and article information

Journal

Journal ID (nlm-journal-id): 101612108

Journal ID (pubmed-jr-id): 41585

Journal ID (nlm-ta): J Carcinog Mutagen

Journal ID (iso-abbrev): J Carcinog Mutagen

Title: Journal of carcinogenesis & mutagenesis

ISSN (Electronic): 2157-2518

Publication date Nihms-submitted: 5 September 2014

Publication date (Electronic): 31 May 2014

Publication date PMC-release: 24 September 2014

Volume: 5

Issue: 3

Electronic Location Identifier: 1000176

Affiliations

[1 ]Comparative Medicine, Messerli Research Institute, University of Veterinary Medicine Vienna, Medical University Vienna, and University Vienna, Vienna, Austria

[2 ]Comparative Immunology and Oncology, Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria

Author notes

[* ] Corresponding author: Prof. Dr. Erika Jensen-Jarolim, Comparative Immunology and Oncology-Institute of Pathophysiology and Allergy Research, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria, Tel: 0043-1-40400-5120; Fax: 0043-1-40400-6188; erika.jensen-jarolim@ 123456meduniwien.ac.at

Article

Manuscript ID: EMS60228

DOI: 10.4172/2157-2518.1000176

PMC ID: 4174352

PubMed ID: 25264496

SO-VID: b0a3075b-b880-417d-ad00-2791b34dbf56

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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

IgE-based Immunotherapy of Cancer -A Comparative Oncology Approach

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Cancer Immunotherapy

Most cited references 142

Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses.

Fcgamma receptors: old friends and new family members.

Feedback regulation of EGFR signalling: decision making by early and delayed loops.

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