title: A novel recombinant immunocasp-6 fusion gene specifically and efficiently             suppresses HER2-overexpressing osteosarcoma.
abstract: Osteosarcoma is the most common primary malignant tumor of bone for adolescent             or children. The poor prognosis of patients, due to its remote metastasis, has             led to the exploration of more effective and less toxic treatments. Immunotherapy             is a promising strategy for the treatment of human epidermal growth factor receptor             2 (HER2)-overexpressing tumors. Herein, we describe experiments conducted with             a fusion gene, immunocasp-6, which was generated by fusing a HER2-specific single-chain             Ab, a single-chain Pseudomonas exotoxin A and an active caspase-6 which can directly             cleave lamin A leading to nucleus damage inducing programmed cell death. We demonstrated             that immunocasp-6 can specifically and efficiently recognize and induce apoptosis             in HER2-overexpressing osteosarcoma cells in vitro. The immunocasp-6 was transferred             into BALB/c athymic mice bearing human osteosarcoma by i.m. injection of liposome-encapsulated             pCMV-immunocap-6. Expression of immunocasp-6 not only strongly inhibited tumor             growth and significantly prolonged animal survival, but also greatly prevented             tumor metastasis. Our data showed that the immuno-casp-6 can specifically recognize             HER2-overexpressing osteosarcoma cells, can also promptly attack their nucleus             and induce apoptotic death, suggesting the potential of this strategy for the             treatment of human HER2-overexpressing tumors.
authors.affiliation: Graduate School of Southern Medical University, Department of Orthopaedics, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, Guangdong, PR China.
authors.forename: Ben-Gen
authors.initials: BG
authors.lastname: Zhou
authors.forename: Mei-Yuan
authors.initials: MY
authors.lastname: Liu
authors.forename: Xiu-Chun
authors.initials: XC
authors.lastname: Qiu
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: Xu
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: Fan
authors.forename: An-Gang
authors.initials: AG
authors.lastname: Yang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Xia
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D001427:Bacterial Toxins / Q000235:genetics; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D053178:Caspase 6 / Q000235:genetics; D049109:Cell Proliferation; D005098:Exotoxins / Q000235:genetics; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D037521:Virulence Factors / Q000235:genetics; D023041:Xenograft Model Antitumor Assays; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D053178:Caspase 6; D005098:Exotoxins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C543058:immunocasp-6