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

J. Singer, G. Achatz-Straussberger, A. Bentley-Lukschal, J. Singer, G. Achatz, S.N. Karagiannis, E. Jensen-Jarolim, World Allergy Organization Journal 12 (2019).


Journal Article | Published | English
Author
Singer, Josef ; Achatz-Straussberger, Gertrude; Bentley-Lukschal, Anna; Singer, JuditIST Austria ; Achatz, Gernot; Karagiannis, Sophia N.; Jensen-Jarolim, Erika
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.
Publishing Year
Date Published
2019-07-29
Journal Title
World Allergy Organization Journal
Volume
12
Issue
7
Article Number
100044
ISSN
IST-REx-ID

Cite this

Singer J, Achatz-Straussberger G, Bentley-Lukschal A, et al. AllergoOncology: High innate IgE levels are decisive for the survival of cancer-bearing mice. World Allergy Organization Journal. 2019;12(7). doi:10.1016/j.waojou.2019.100044
Singer, J., Achatz-Straussberger, G., Bentley-Lukschal, A., Singer, J., Achatz, G., Karagiannis, S. N., & Jensen-Jarolim, E. (2019). AllergoOncology: High innate IgE levels are decisive for the survival of cancer-bearing mice. World Allergy Organization Journal, 12(7). https://doi.org/10.1016/j.waojou.2019.100044
Singer, Josef, Gertrude Achatz-Straussberger, Anna Bentley-Lukschal, Judit Singer, Gernot Achatz, Sophia N. Karagiannis, and Erika Jensen-Jarolim. “AllergoOncology: High Innate IgE Levels Are Decisive for the Survival of Cancer-Bearing Mice.” World Allergy Organization Journal 12, no. 7 (2019). https://doi.org/10.1016/j.waojou.2019.100044.
J. Singer et al., “AllergoOncology: High innate IgE levels are decisive for the survival of cancer-bearing mice,” World Allergy Organization Journal, vol. 12, no. 7, 2019.
Singer J, Achatz-Straussberger G, Bentley-Lukschal A, Singer J, Achatz G, Karagiannis SN, Jensen-Jarolim E. 2019. AllergoOncology: High innate IgE levels are decisive for the survival of cancer-bearing mice. World Allergy Organization Journal. 12(7).
Singer, Josef, et al. “AllergoOncology: High Innate IgE Levels Are Decisive for the Survival of Cancer-Bearing Mice.” World Allergy Organization Journal, vol. 12, no. 7, 100044, Elsevier, 2019, doi:10.1016/j.waojou.2019.100044.
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