http://informahealthcare.com/ipi ISSN: 0892-3973 (print), 1532-2513 (electronic) Immunopharmacol Immunotoxicol, Early Online: 1–6 ! 2015 Informa Healthcare USA, Inc. DOI: 10.3109/08923973.2015.1027917 RESEARCH ARTICLE Cancer immunotherapy by a recombinant phage vaccine displaying EGFR mimotope: an in vivo study Majid Asadi-Ghalehni 1 , Mohamad Ghaemmaghami 1 , Alexander Klimka 2 , Masoud Javanmardi 1 , Mohsen Navari 1 , and Mohammad Javad Rasaee 1 1 Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran and 2 Institute of Medical Microbiology, Immunology and Hygiene IMMIH, University Hospital of Cologne, Cologne, Germany Abstract To date, several small molecule inhibitors and monoclonal-antibodies (like ICR-62) have been used to treat tumors over-expressing epidermal growth factor receptor (EGFR). However, the limitations associated with these conventional applications accentuate the necessity of alternative approaches. Mimotopes as compelling molecular tools could rationally be employed to circumvent these drawbacks. In the present study, an M13 phage displaying ICR-62 binding peptide mimotope is exploited as a vaccine candidate. It exhibited high affinity towards ICR62 and polyclonal anti-P-BSA antibodies. Following the mice immunization, phage- based mimotope vaccine induced humoral immunity. Elicited anti-EGFR mimotope antibodies were detected using ELISA method. Moreover, the phage vaccine was tested on the Lewis lung carcinoma mice model to investigate the prophylactic and therapeutic effects. The tumor volume was measured and recorded in different animal groups to evaluate the anti-tumor effects of the vaccine. Our data indicate that the reported phage-based mimotope could potentially elicit specific antibodies resulting in low titers of EGFR-specific antibodies and reduced tumor growth. However, in vivo experiments of prophylactic or therapeutic vaccination showed no specific advantage. Furthermore, phage-mimotope vaccine might be a promising approach in the field of cancer immunotherapy. Keywords EGFR, mimotope, phage vaccine, prophylactic and therapeutic potentials History Received 10 December 2014 Revised 25 February 2015 Accepted 7 March 2015 Published online 20 May 2015 Introduction Epidermal growth factor receptor (EGFR) is a member of HER family tyrosine kinase receptors with intrinsic tyrosine kinase activity, playing pivotal roles in the regulation of cellular survival, proliferation, differentiation and migration. Their oncogenic potential has been proven by the fact that their over expression is marked by tumor progression, invasiveness and angiogenesis. Moreover, their over expres- sion have been found in many human malignancies including different forms of carcinoma and even glioblastomas to name but a few. The significance of signaling pathways, HER family tyrosine kinase receptors involved in, along with their ubiquitous expression in different types of tumors have explicitly made them to be as an attractive target for specific cancer therapy 1–3 . Over the past decades, numerous strategies of cancer therapy have been developed with EGFR as their primary target. These methods include application of small molecule tyrosine kinase inhibitors as well as monoclonal antibodies 3,4 . Several monoclonal antibodies have been successfully used to treat cancer patients and many of these antibodies have received FDA’s approval 5,6 . However, there are some limita- tions associated with the clinical applications of monoclonal antibodies including necessity of repetitive administration to achieve consistent and effective dose and their high prices that makes them unavailable for most cancer patients and existence of non-human parts which can elicit host immune responses, remarkably reducing their circulation period 7,8 . However, small molecules drugs have some problems like biocompatibility, stability and pharmacokinetics 9,10 . Active immunization against a particular cancer antigen can be considered as a viable alternative to monoclonal antibodies. These methods can ideally stimulate patient’s immune system to mount a response, against a given cancer antigen, which can eradicate the disease and prevent its recurrence for the rest of the patient’s life 11 . Dong et al. evaluated the efficiency of the T7 phage vaccine displaying different epitopes of EGFR against the EGFR-positive tumor. Since the antibodies produced against different epitopes of the tumor antigens, such as EGFR, can exert opposing effects on tumor cell growth (some of them may inhibit tumor growth while others may stimulate it) 12 , epitope specificity is of essential importance in designing effective cancer vaccines. Address for correspondence: Mohammad Javad Rasaee, Department of Medical Biotechnology, School of Medical Sciences, Tarbiat Modares University, Chamran Jalal Crossing, PO Box 14115-331, Tehran, Iran. Tel: +98 21 82884513. E-mail: Rasaee_m@modares.ac.ir Immunopharmacology and Immunotoxicology Downloaded from informahealthcare.com by 194.225.170.211 on 05/20/15 For personal use only.