IGKC and FcγR genotypes and humoral immunity to HER2 in breast cancer

Pandey, Janardan P.; Kistner-Griffin, Emily; Black, Laurel; Namboodiri, Aryan M.; Iwasaki, Motoki; Kasuga, Yoshio; Hamada, Gerson Shigueaki; Tsugane, Shoichiro

doi:10.1016/j.imbio.2013.08.005

Cited by 22 publications

(18 citation statements)

References 17 publications

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“…Anti-tumor marker specific antibodies may be detectable in cancer patients which indicate the role of humoral immunity in tumor destruction 22 . The anti-tumor activity of monoclonal antibodies has shown clinical success in treatment of different kinds of cancers 1,23-25 , but high concentrations of these reagents and their immunogenicity of repeatedly administration reveals the necessity of applying a suitable immunogenic agent for raising active immunity 26,27 .…”

Section: Discussionmentioning

confidence: 99%

Epitope mapping of epidermal growth factor receptor (EGFR) monoclonal antibody and induction of growth-inhibitory polyclonal antibodies by vaccination with EGFR mimotope

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Javanmardi

et al. 2014

Immunopharmacology and Immunotoxicology

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One of the proposed approaches in cancer therapy is to induce and direct the patient's own immune system against cancer cells. In this study, we determined the epitope mapping of the rat anti-human epidermal growth factor receptor (EGFR) monoclonal antibody ICR-62 using a phage display of random peptide library and identified a 12 amino acids peptide, which was recognized as a mimotope. The peptide was synthesized and conjugated to bovine serum albumin (BSA) as carrier protein (P-BSA). We have shown that ICR-62 can react specifically with P-BSA as well as native EGFR. Two rabbits were immunized either by BSA or P-BSA and the rabbits IgGs were purified and examined for binding to the antigens, mimotope and the EGFR protein purified from the EGFR overexpressing A431 cell line. We showed that the rabbit IgG generated against the mimotope is capable of inhibiting the growth of A431 cells by 15%, but does not have any effect on the growth of EGFR-negative MDA-MB-453 cell line in vitro. Our results support the need for further investigations on the potential of vaccination with either mimotope of the EGFR or epitope displayed on the surface of phage particles for use in active immunotherapy of cancer.

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Section: Discussionmentioning

confidence: 99%

Epitope mapping of epidermal growth factor receptor (EGFR) monoclonal antibody and induction of growth-inhibitory polyclonal antibodies by vaccination with EGFR mimotope

Navari

Zare

Javanmardi

et al. 2014

Immunopharmacology and Immunotoxicology

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“…The KM 1,3 alleles were previously determined (Pandey et al, 2014), by a PCR-RFLP method (Moxley and Gibbs, 1992). …”

Section: Methodsmentioning

confidence: 99%

Endogenous antibody responses to mucin 1 in a large multiethnic cohort of patients with breast cancer and healthy controls: Role of immunoglobulin and Fcγ receptor genes

et al. 2018

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High levels of naturally occurring IgG antibodies to mucin 1 (MUC1), a membrane-bound glycoprotein that is overexpressed in patients with breast cancer, are associated with good prognosis. This suggests that endogenous anti-MUC1 antibodies have a protective effect and, through antibody-mediated host immunosurveillance mechanisms, might contribute to a cancer-free state. To test this possibility, we characterized a large number of multiethnic patients with breast cancer and matched controls for IgG antibodies to MUC1. We also aimed to determine whether the magnitude of anti-MUC1 antibody responsiveness was associated with particular immunoglobulin GM (γ marker), KM (κ marker), and Fcγ receptors (FcγR) genotypes. After adjusting for the confounding variables in a multivariate analysis, we found no significant difference in the levels of anti-MUC1 IgG antibodies between patients and cancer-free controls. However, in patients and controls, particular GM, KM, and FcγR genotypes—individually or epistatically—were significantly associated with the levels of anti-MUC1 IgG antibodies in a racially restricted manner. These findings, if confirmed in an independent investigation, could help identify individuals most likely to benefit from a MUC1-based therapeutic or prophylactic vaccine for MUC1-overexpressing malignancies.

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“…However, this effect has not been further confirmed in subsequent larger cohorts, compromising the predictive value of this polymorphism on trastuzumab resistance [95,97]. In fact, FCGR2A-131 H/H genotype has only demonstrated influence on antibody responsiveness to HER2 in determinate ethnicities (Table 5) [96,98].…”

Section: Tumor Host Factorsmentioning

confidence: 99%

De Novo Resistance Biomarkers to Anti-Her2 Therapies in Her2-Positive Breast Cancer

et al. 2015

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Therapies targeting HER2 receptor, overexpressed in 20% breast cancer (BC), improved prognosis, however ~62% patients experiment progression during the first year. Molecular mechanisms proposed to be responsible for this de novo resistance include HER2 modifications, defects in the antibody dependent cellular cytotoxicity or in cell arrest and apoptosis or alterations in HER2 signaling components. This article will review the influence of genetic markers investigated to date as cause of de novo resistance to HER2-targeted drugs in HER2-positive BC patients. Biomarkers like p95HER2, CCND1 and CDC25A have demonstrated clinical relevance and prognostic value in HER2-positive BC patients. However, the prognostic value of most biomarkers investigated to date, such as PIK3CA or AKT1, cannot be fully established yet.

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IGKC and FcγR genotypes and humoral immunity to HER2 in breast cancer

Cited by 22 publications

References 17 publications

Epitope mapping of epidermal growth factor receptor (EGFR) monoclonal antibody and induction of growth-inhibitory polyclonal antibodies by vaccination with EGFR mimotope

Epitope mapping of epidermal growth factor receptor (EGFR) monoclonal antibody and induction of growth-inhibitory polyclonal antibodies by vaccination with EGFR mimotope

Endogenous antibody responses to mucin 1 in a large multiethnic cohort of patients with breast cancer and healthy controls: Role of immunoglobulin and Fcγ receptor genes

De Novo Resistance Biomarkers to Anti-Her2 Therapies in Her2-Positive Breast Cancer

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