Epitope mapping of epidermal growth factor receptor (EGFR) monoclonal antibody and induction of growth-inhibitory polyclonal antibodies by vaccination with EGFR mimotope
Authors:
- Mehrak ZareMZMehrak Zare
- Masoud JavanmardiMJMasoud Javanmardi
- Majid Asadi-GhalehniMAMajid Asadi-Ghalehni
- Helmout ModjtahediHMHelmout Modjtahedi
- Mohammad Javed RasaeeMRMohammad Javed Rasaee
- 29 July 2014
- journal article
- Published by Taylor & Francis in Immunopharmacology and Immunotoxicology
- Vol. 36 (5) , 309-315
Abstract
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.Keywords
This publication has 34 references indexed in Scilit:
- Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced CancerNew England Journal of Medicine, 2012
- Intra-tumour heterogeneity: a looking glass for cancer?Nature Reviews Cancer, 2012
- Generation and characterization of peptide mimotopes specific for anti ErbB-2 monoclonal antibodiesInternational Immunology, 2011
- Peptide mimotopes recognized by antibodies cetuximab and matuzumab induce a functionally equivalent anti-EGFR immune responseOncogene, 2010
- Epidermal growth factor receptor expression in breast cancer association with biologic phenotype and clinical outcomesCancer, 2010
- Clinical Applications of a Peptide-Based Vaccine for GlioblastomaNeurosurgery Clinics of North America, 2010
- Predictive value of EGFR and HER2 overexpression in advanced non-small-cell lung cancerOncogene, 2009
- Mimotope vaccination – from allergy to cancerExpert Opinion on Biological Therapy, 2009
- Mimotope vaccines: Epitope mimics induce anti-cancer antibodiesImmunology Letters, 2007
- Phase I study of the humanised anti-EGFR monoclonal antibody matuzumab (EMD 72000) combined with gemcitabine in advanced pancreatic cancerBritish Journal of Cancer, 2006