Asadi-Ghalehni Majid, Ghaemmaghami Mohamad, Klimka Alexander, Javanmardi Masoud, Navari Mohsen, Rasaee Mohammad Javad
Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University , Tehran , Iran and.
Immunopharmacol Immunotoxicol. 2015 Jun;37(3):274-9. doi: 10.3109/08923973.2015.1027917. Epub 2015 May 20.
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.
迄今为止,几种小分子抑制剂和单克隆抗体(如ICR - 62)已被用于治疗过度表达表皮生长因子受体(EGFR)的肿瘤。然而,这些传统应用的局限性凸显了采用替代方法的必要性。模拟表位作为引人注目的分子工具,可以合理地用于规避这些缺点。在本研究中,展示ICR - 62结合肽模拟表位的M13噬菌体被用作候选疫苗。它对ICR62和多克隆抗P - BSA抗体表现出高亲和力。在小鼠免疫后,基于噬菌体的模拟表位疫苗诱导了体液免疫。使用ELISA方法检测到引发的抗EGFR模拟表位抗体。此外,在Lewis肺癌小鼠模型上测试了噬菌体疫苗,以研究其预防和治疗效果。测量并记录不同动物组的肿瘤体积,以评估疫苗的抗肿瘤效果。我们的数据表明,所报道的基于噬菌体的模拟表位可能潜在地引发特异性抗体,导致低滴度的EGFR特异性抗体并减少肿瘤生长。然而,预防性或治疗性疫苗接种的体内实验未显示出特定优势。此外,噬菌体模拟表位疫苗可能是癌症免疫治疗领域中一种有前景的方法。