AllergoOncology: High innate IgE levels are decisive for the survival of cancer-bearing mice.
World Allergy Organ J
; 12(7): 100044, 2019.
Article
em En
| MEDLINE
| ID: mdl-31388397
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.
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
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
World Allergy Organ J
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Áustria