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World Allergy Organ J. 2019 Jul 29;12(7):100044. doi: 10.1016/j.waojou.2019.100044. eCollection 2019.

AllergoOncology: High innate IgE levels are decisive for the survival of cancer-bearing mice.

Author information

1
Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University Vienna, Austria.
2
Department of Internal Medicine II, University Hospital Krems, Karl, Landsteiner University of Health Sciences, Krems an der Donau, Austria.
3
The Interuniversity Messerli Research Institute of the University of Veterinary Medicine Vienna, Medical University Vienna and University Vienna, Austria.
4
Department of Molecular Biology, University of Salzburg, Austria.
5
St. John's Institute of Dermatology, School of Basic and Medical Biosciences, King's College London, Guy's Hospital; London, UK.
6
Division of Cancer Studies, Faculty of Life Sciences & Medicine;King's College London, Guy's Hospital, London, UK.

Abstract

Background:

Atopics have a lower risk for malignancies, and IgE targeted to tumors is superior to IgG in fighting cancer. Whether IgE-mediated innate or adaptive immune surveillance can confer protection against tumors remains unclear.

Objective:

We aimed to investigate the effects of active and passive immunotherapy to the tumor-associated antigen HER-2 in three murine models differing in Epsilon-B-cell-receptor expression affecting the levels of expressed IgE.

Methods:

We compared the levels of several serum specific anti-HER-2 antibodies (IgE, IgG1, IgG2a, IgG2b, IgA) and the survival rates in low-IgE ΔM1M2 mice lacking the transmembrane/cytoplasmic domain of Epsilon-B-cell-receptors expressing reduced IgE levels, high-IgE KN1 mice expressing chimeric Epsilon-Gamma1-B-cell receptors with 4-6-fold elevated serum IgE levels, and wild type (WT) BALB/c. Prior engrafting mice with D2F2/E2 mammary tumors overexpressing HER-2, mice were vaccinated with HER-2 or vehicle control PBS using the Th2-adjuvant Al(OH)3 (active immunotherapy), or treated with the murine anti-HER-2 IgG1 antibody 4D5 (passive immunotherapy).

Results:

Overall, among the three strains of mice, HER-2 vaccination induced significantly higher levels of HER-2 specific IgE and IgG1 in high-IgE KN1, while low-IgE ΔM1M2 mice had higher IgG2a levels. HER-2 vaccination and passive immunotherapy prolonged the survival in tumor-grafted WT and low-IgE ΔM1M2 strains compared with treatment controls; active vaccination provided the highest benefit. Notably, untreated high-IgE KN1 mice displayed the longest survival of all strains, which could not be further extended by active or passive immunotherapy.

Conclusion:

Active and passive immunotherapies prolong survival in wild type and low-IgE ΔM1M2 mice engrafted with mammary tumors. High-IgE KN1 mice have an innate survival benefit following tumor challenge.

KEYWORDS:

ADCC, Antibody-dependent Cell-mediated Cytotoxicity; ADCP, Antibody-dependent Cellular Phagocytosis; AllergoOncology; BCR, B-Cell Receptor; Cancer vaccine; HER-2; HER-2, Human Epidermal Growth Factor Receptor-2, ErbB-2; IgA, Immunoglobulin A; IgE; IgE, Immunoglobulin E; IgG, Immunoglobulin G; Onco-immunology; TAA, Tumor-Associated Antigen; WT, wild type

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