title: A novel recombinant protein of IP10-EGFRvIIIscFv and CD8(+) cytotoxic T lymphocytes synergistically inhibits the growth of implanted glioma in mice.
abstract: The epidermal growth factor receptor (EGFR) mutant of EGFRvIII is highly expressed on glioma cells and has been thought to be an excellent target molecule for immunotherapy. IP-10 is a potent chemokine and can recruit CXCR3(+) T cells, including CD8(+) T cells that are important for the control of tumor growth. This study is aimed at investigating the therapeutic efficacy of a novel fusion protein of IP10-EGFRvIIIscFv (IP10-scFv) in combination with glioma lysate-pulsed DCs-activated CD8(+) cytotoxic T lymphocytes (CTLs) in a mouse model of glioma. A plasmid of pET-IP10-scFv was generated by linking mouse IP-10 gene with the DNA fragment for anti-EGFRvIIIscFv, a (Gly4Ser)3 flexible linker and a His-tag. The recombinant IP10-scFv in E. coli was purified by affinity chromatography and characterized for its anti-EGFRvIII immunoreactivity and chemotactic activity. C57BL/6 mice were inoculated with mouse glioma GL261 cells in the brain and treated intracranially with IP10-scFv and/or intravenously with CTL for evaluating the therapeutic effect. The glioma-specific immune responses were examined. The IP10-scFv retained anti-EGFRvIII immunoreactivity and IP-10-like chemotactic activity. Treatment with both IP10-scFv and CTL synergistically inhibited the growth of glioma and prolonged the survival of tumor-bearing mice, accompanied by increasing the numbers of brain-infiltrating lymphocytes (BILs) and the frequency of CXCR3(+)CD8(+) T cells, enhancing glioma-specific IFN-γ responses and cytotoxicity, and promoting glioma cell apoptosis in mice. Our novel data indicate that IP10-scFv and CTL have synergistic therapeutic effects on inhibiting the growth of mouse glioma in vivo.
authors: Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China.
authors: Xuan
authors: X
authors: Wang
authors: Xiao-Ling
authors: XL
authors: Lu
authors: Hong-Yang
authors: HY
authors: Zhao
authors: Fang-Cheng
authors: FC
authors: Zhang
authors: Xiao-Bing
authors: XB
authors: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000276:immunology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000235:genetics / Q000276:immunology*; D005260:Female; D005910:Glioma / Q000276:immunology / Q000628:therapy*; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
chemical_list: C104577:IP10-Mig receptor; D018121:Receptors, Cytokine; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors
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