Asadi-Ghalehni Majid, Rasaee Mohamad Javad, Namvar Asl Nabiollah, Khosravani Masood, Rajabibazl Masoumeh, Khalili Saeed, Modjtahedi Helmout, Sadroddiny Esmaeil
Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Iran J Allergy Asthma Immunol. 2018 Jun;17(3):240-249.
Over expression of the epidermal growth factor receptor (EGFR) in many human epithelial tumors has been correlated with disease progression and poor prognosis. EGFR-inhibiting immunotherapy has already been introduced in cancer therapy. Peptide displaying phage particles in eukaryotic hosts can behave as antigen carriers, able to activate the innate immune system and to elicit adaptive immunity. Herein, the M13-pAK8-VIII phagemid plasmid was engineered to contain the sequences for an EGFR mimotope along with the L2 extracellular domain of EGFR (EM-L2) which would produce the final peptide-phage vaccine. The prophylactic and therapeutic effects of this novel vaccine were evaluated on the Lewis lung carcinoma induced mouse (C57/BL6) model. The recombinant peptide was confirmed to be displayed on the surface of M13 phage as an extension for phage's PVIII protein. Immunization of mice with peptide-phage vaccine resulted in antibody production against EM-L2 and significant reduction of tumor growth rate by nearly 25 percent. In conclusion, EM-L2 displaying phage particles could be deemed as an encouraging strategy in contemporary cancer immunotherapy.
表皮生长因子受体（EGFR）在许多人类上皮肿瘤中的过表达与疾病进展和不良预后相关。EGFR抑制性免疫疗法已被引入癌症治疗。在真核宿主中展示噬菌体颗粒的肽可作为抗原载体，能够激活先天免疫系统并引发适应性免疫。在此，对M13-pAK8-VIII噬菌粒质粒进行改造，使其包含EGFR模拟表位的序列以及EGFR的L2细胞外结构域（EM-L2），这将产生最终的肽-噬菌体疫苗。在Lewis肺癌诱导的小鼠（C57/BL6）模型上评估了这种新型疫苗的预防和治疗效果。重组肽被证实作为噬菌体PVIII蛋白的延伸展示在M13噬菌体表面。用肽-噬菌体疫苗免疫小鼠可产生针对EM-L2的抗体，并使肿瘤生长速率显著降低近25%。总之，展示EM-L2的噬菌体颗粒可被视为当代癌症免疫治疗中一种令人鼓舞的策略。
