Triple tandem mimotope peptide of epidermal growth factor receptor displaying on the surface of M13 phage induces anti-tumor response in mice tumor model

Epidermal growth factor receptor [EGFR] has been shown to play a critical role in tumor cell growth and its over expression has been observed in many epithelial tumors. In the field of cancer vaccine research, displaying the peptide mimotope on the surface of phage particles has shown promising results. In this study using m13-PVIII phage display system, two constructions were prepared: triple tandem repeat of EGFR mimotpe displaying particles [3M] and single EGFR mimotope displaying phage particle [1M]. To investigate the anti-tumor properties of phage vaccine, C57BL/6 mice Lewis lung carcinoma xenograft model was established and treated with 3M phage vaccine, 1M phage vaccine and control agents. Immunization of mice with these phage-based vaccines showed strong immune response against phage-mimotope. 3M phage vaccine showed more potency against tumor in comparison with control groups. Also the survival time was extended in phage vaccine treated tumor-bearing mice compared with untreated mice. Our findings suggest that mimotope-displaying phage vaccine can induce specific antibodies with antitumoral activity, which its potential as a candidate vaccine for EGFR-specific cancer immunotherapy needs to be more investigated in future studies

Production and characterization of a monoclonal antibody against an antigen on the surface of non-small cell carcinoma of the lung

Lung carcinoma is a multiple type cancer comprising of small cell and non-small cell carcinomas [NSCLC]. For therapeutic and diagnostic purposes, serum monoclonal antibodies have been produced against lung cancer. To characterize a murine monoclonal antibody [ME3D11] reactive with human NSCLC. A murine monoclonal antibody [ME3D11] reactive with human NSCLC was selected after immunization of BALB/c mice with a human large cell carcinoma with neuroendocrine differentiation, and was tested by immunofloursence staining and Western blot analysis. Our study showed that the antigen recognized by ME3D11 antibody was a cell surface antigen of 170kDa. This antigen is expressed on the cell surface of all NSCLC and a few carcinoma cell lines. In contrast, this antigen is neither expressed on the cell surface of human sarcoma, nor on the hematopoietic and normal cell lines. This antibody had no effect on spontaneous proliferation of Mehr-80 cell line in vitro. High degree of binding of this monoclonal antibody to NSCLC and some other carcinoma cells warrants further studies on its potential use in diagnosis and therapy of cancer by conjugation to drugs, toxins or radionuclides

Monoclonal antibodies as therapeutic agents: advances and challenges

Despite the major advances in conventional forms of treatment [i.e. surgical techniques, radiotherapy and chemotherapy] and improved survival rates, cancer is still the second leading cause of death in developing countries. One major limitation of cytotoxic drugs and radiation in the treatment of cancer patients is their inability to discriminate between malignant and normal tissues. This in turn prevents the delivery of the optimal [therapeutic] dose of such agents to malignant tissues for their eradication. With the advent of hybridoma technology in 1975, it has been possible for the first time to produce large amounts of an antibody [i.e. monoclonal antibody] against any antigens of interest. Since each antibody is highly specific for a particular antigen, this typical feature of the antibodies has resulted in their widespread use in diagnostic kits, medical research [e.g. to unravel the function of the antigen in physiological and pathological conditions], and more recently, for the management of a wide range of human diseases such as autoimmune disease and human cancers. Thanks to recent advances in genetic engineering, the immunogenicity of rodent antibodies was reduced by producing the chimeric or humanized version of such antibodies or by developing the fully human antibodies. In other instances, as intact antibodies are too large for rapid penetration into solid tumours, it has been possible to develop a smaller fragment of such antibodies [e.g. Fab, scFv, VHH] with greater potential for use in cancer imaging and therapy. Depending on the target antigens and the antibody format, monoclonal antibodies can induce their anti-tumour activities by several mechanisms including activation of the host effector cells. To date, several mAbs have been approved for management of human cancers including: anti-EGFR antibody cetuximab and anti-VEGF antibody bevacizumab for treatment of metastatic colorec-tal cancer, anti-HER-2 antibody trastuzumab for metastatic breast cancer, anti-CD20 antibodies rituximab and ibritumomab tituxetan for non-Hodgkin lymphoma, anti-CD52 antibody alemeutumab for chronic lymphocytic leukaemia, and anti-CD33 antibody gemutuzumab ozogamicin for the treatment of acute myeloid leukaemia patients. Monoclonal antibodies currently account for about 30% of all new drugs in development, with more than 500 antibodies at different stages of clinical trials worldwide. In this review, the characteristic features of some of the therapeutic antibodies and the antigens recognised by such antibodies will be discussed as well as several challenges that need to be addressed in order to facilitate their widespread use as "magic bullets" in the management of human diseases and in particular human cancers

Serum level of HER 2 extracellular domain in Iranian patients with breast cancer: a follow up study

A soluble form of HER-2/neu extracellular domain [sHER-2] is reported to be released in the sera of metastatic breast cancer patients. To measure the level of sHER-2 in sera of 115 breast cancer patients. Serial samples of 27 patients with metastasis, 18 non-metastatic patients, 15 patients in stage 0/I and 14 patients with accompanying benign breast disease were also included in this study. No significant difference was observed between sHER-2 level in the pre-operative sera of breast cancer patients and that of healthy individuals. Only 8 out of 27 patients whom later developed metastasis showed elevated levels of sHER-2 in their first serum sample. However, a trend of increase in the level of sHER-2 was observed in 14 [51.8%] of 27 metastatic sera before clinical diagnosis of the metastasis. A significant association between sHER-2 positive status and vascular invasion of the tumor was observed [P = 0.02]. In addition, significant correlation of sHER-2 level with CEA [highest r = 0.74] and CA 15.3 [highest r = 0.74] tumor marker levels in the serial sera were observed. The mean time from sHER-2 positivity to tumor metastasis was calculated to be 98 days [range = 29-174]. Our results indicate that a relatively high percentage of Iranian patients with breast cancer show an elevated level of sHER-2 in their sera before clinical diagnosis of the tumor metastasis. Therefore, measuring the level of this oncoprotein, not only helps physicians in monitoring the patients during HERCEPTINTM therapy, but also can be helpful in choosing more aggressive treatments at the early satges of tumor metastasis