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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.

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



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.


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.


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).


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.


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.


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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