title: Gene therapy for colorectal cancer using adenovirus-mediated full-length antibody, cetuximab.
abstract: Cetuximab is a chimeric monoclonal antibody, approved to treat patients with metastatic colorectal cancer (mCRC), head and neck squamous cell carcinoma (HNSCC), non-small-cell lung cancer (NSCLC) for years. It functions by blocking the epidermal growth factor receptor (EGFR) from receiving signals or interacting with other proteins. Although the demand for cetuximab for the treatment of cancer patients in clinics is increasing, the complicated techniques involved and its high cost limit its wide applications. Here, a new, cheaper form of cetuximab was generated for cancer gene therapy. This was achieved by cloning the full-length cetuximab antibody into two serotypes of adenoviral vectors, termed as AdC68-CTB and Hu5-CTB. In vivo studies showed that a single dose of AdC68-CTB or Hu5-CTB induced sustained cetuximab expression and dramatically suppressed tumor growth in NCI-H508- or DiFi-inoculated nude mice. In conclusion, gene therapy using adenovirus expressing full-length cetuximab could be a novel alternative method for the effective treatment of colorectal cancer.
authors.affiliation: Vaccine Research Center, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Science, Shanghai, China.
authors.forename: Man
authors.initials: M
authors.lastname: Xing
authors.affiliation: Vaccine Research Center, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Science, Shanghai, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Vaccine Research Center, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Science, Shanghai, China.
authors.forename: Yudan
authors.initials: Y
authors.lastname: Chi
authors.affiliation: Vaccine Research Center, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Science, Shanghai, China.
authors.forename: Dongming
authors.initials: D
authors.lastname: Zhou
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000068818:Cetuximab / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000473:pathology*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D000068818:Cetuximab
keywords: EGFR; adenovirus; cetuximab; colorectal cancer; gene therapy