The application of phage display technique in oral cancer treatment

• Main Authors: Chun-fu Wang, 王俊富
• Other Authors: Sen-Tien Tsai
• Format: Others
• Language: en_US
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/5zm623

碩士 === 國立中山大學 === 生物醫學科學研究所 === 95 === Phage display is a molecular technique accomplished by incorporation of the nucleotide sequence encoding the protein to be displayed into a phage or phagemid genome as a fusion to a gene encoding a phage coat protein. After several rounds of selection and amplification, high affinity phage clones, and thus high affinity “homing peptides” can be obtained. Cell-binding homing peptides selected in this manner could be linked by physical or genetic manipulation to gene therapy vectors that mediate their own entry (viral or non-viral vectors) to facilitate targeting. Homing peptides that target specific cellular receptors can also be used as a treatment modality to induce various signal transduction pathways or even apoptotic signals of cancer cells. Oral squamous cell carcinoma (OSCC) is one of the most common cancers in the world. It has become the fourth cancer death reason of males in Taiwan. Radical surgery combined with postoperative chemotherapy and/or radiotherapy is still the major modality for treatment of OSCC. The 5-year survival rate of OSCC is still discouraged in recent years. Patients with OSCC present numerous challenges to treating physicians. In this study, we aimed to isolate and identify homing phage clones specific to oral cancer cells by panning with a random phage peptide library. The homing phage clones will be used as a basis to improve targeting specificity of gene therapy vectors. A NCBI BLAST search was performed and close similarities were found to several important molecules biologically with the homing peptides carried by phage clones. Characterization of the selected phage-29 was then studied by immunohistochemical methods. Internalization of this phage-29 is sequence-specific and mediated by integrin αvβ6 in HSC-3 cells rapidly. We also confirmed that the integrin αvβ6-targeting homing peptide is universally useful in all major kinds of head and neck cancer. We will further study the possible biological functions of the other homing peptides to see whether these peptides could have potential applications for oral cancer treatment.