title: Human IP10-scFv and DC-induced CTL synergistically inhibit the growth of glioma in a xenograft model.
abstract: The epidermal growth factor receptor (EGFR) mutant of EGFRvIII is highly expressed in glioma cells, and the EGFRvIII-specific dendritic cell (DC)-induced tumor antigen-specific CD8(+) cytotoxic T lymphocytes (CTLs) may hold promise in cancer immunotherapy. Interferon (IFN)-γ-inducible protein (IP)-10 (IP-10) is a potent inhibitor of angiogenesis and can recruit CXCR3(+) T cells, including CD8(+) T cells, which are important for the control of tumor growth. In this study, we assessed if the combination of IP10-EGFRvIIIscFv with DC-induced CTLs would improve the therapeutic antitumor efficacy. IP10-scFv was generated by linking the human IP-10 gene with the DNA fragment for anti-EGFRvIIIscFv with a (Gly4Ser)3 flexible linker, purified by affinity chromatography, and characterized for its anti-EGFRvIII immunoreactivity and chemotactic activity. DCs were isolated from human peripheral blood monocyte cells and pulsed with EGFRvIII-peptide, then co-cultured with autologous CD8(+) T cells. BALB/c-nu mice were inoculated with human glioma U87-EGFRvIII cells in the brain and treated intracranially with IP10-scFv and/or intravenously with DC-induced CTLs for evaluating the therapeutic effect. Treatment with both IP10-scFv and EGFRvIII peptide-pulsed, DC-induced CTL synergistically inhibited the growth of glioma and prolonged the survival of tumor-bearing mice, which was accompanied by the inhibition of tumor angiogenesis and enhancement of cytotoxicity, thereby increasing the numbers of brain-infiltrating lymphocytes (BILs) and prolonging the residence time of CTLs in the tumor.
authors.affiliation: Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.forename: Fang-Cheng
authors.initials: FC
authors.lastname: Zhang
authors.forename: Hong-Yang
authors.initials: HY
authors.lastname: Zhao
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Lu
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Xiong
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D054357:Chemokine CXCL10 / Q000235:genetics*; D003713:Dendritic Cells / Q000276:immunology*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D057809:HEK293 Cells; D006801:Humans; D016219:Immunotherapy, Adoptive; D051379:Mice; D008807:Mice, Inbred BALB C; D041681:NIH 3T3 Cells; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000627:therapeutic use*; D057127:Single-Chain Antibodies / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies; D066246:ErbB Receptors