PMID- 18670452 OWN - NLM STAT- MEDLINE DCOM- 20090310 LR - 20231120 IS - 1476-5500 (Electronic) IS - 0929-1903 (Linking) VI - 16 IP - 2 DP - 2009 Feb TI - TNF-alpha and the IFN-gamma-inducible protein 10 (IP-10/CXCL-10) delivered by parvoviral vectors act in synergy to induce antitumor effects in mouse glioblastoma. PG - 149-60 LID - 10.1038/cgt.2008.62 [doi] AB - Interferon-gamma-inducible protein 10 is a potent chemoattractant for natural killer cells and activated T lymphocytes. It also displays angiostatic properties and some antitumor activity. Tumor necrosis factor-alpha (TNF-alpha) is a powerful immunomodulating cytokine with demonstrated tumoricidal activity in various tumor models and the ability to induce strong immune responses. This prompted us to evaluate the antitumor effects of recombinant parvoviruses designed to deliver IP-10 or TNF-alpha into a glioblastoma. When Gl261 murine glioma cells were infected in vitro with an IP-10- or TNF-alpha-transducing parvoviral vector and were subcutaneously implanted in mice, tumor growth was significantly delayed. Complete tumor regression was observed when the glioma cells were coinfected with both the vectors, demonstrating synergistic antitumor activity. In an established in vivo glioma model, however, repeated simultaneous peritumoral injection of the IP-10- and TNF-alpha-delivering parvoviruses failed to improve the therapeutic effect as compared with the use of a single cytokine-delivering vector. In this tumor model, cytokine-mediated immunostimulation, rather than inhibition of vascularization, is likely responsible for the therapeutic efficacy. FAU - Enderlin, M AU - Enderlin M AD - Deutsches Krebsforschungszentrum, Infection and Cancer Program, Heidelberg, Germany. FAU - Kleinmann, E V AU - Kleinmann EV FAU - Struyf, S AU - Struyf S FAU - Buracchi, C AU - Buracchi C FAU - Vecchi, A AU - Vecchi A FAU - Kinscherf, R AU - Kinscherf R FAU - Kiessling, F AU - Kiessling F FAU - Paschek, S AU - Paschek S FAU - Sozzani, S AU - Sozzani S FAU - Rommelaere, J AU - Rommelaere J FAU - Cornelis, J J AU - Cornelis JJ FAU - Van Damme, J AU - Van Damme J FAU - Dinsart, C AU - Dinsart C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080801 PL - England TA - Cancer Gene Ther JT - Cancer gene therapy JID - 9432230 RN - 0 (CXCL10 protein, human) RN - 0 (Chemokine CXCL10) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Chemokine CXCL10/administration & dosage/immunology/*metabolism/*therapeutic use MH - Dendritic Cells/cytology/virology MH - Drug Synergism MH - Female MH - Genetic Vectors MH - Glioblastoma/blood supply/*drug therapy/immunology/metabolism/virology MH - H-1 parvovirus/physiology MH - Humans MH - Immunocompetence MH - Mice MH - Mice, Inbred C57BL MH - Minute Virus of Mice/physiology MH - Necrosis/metabolism MH - Tumor Cells, Cultured/cytology/drug effects MH - Tumor Necrosis Factor-alpha/administration & dosage/genetics/*metabolism/*therapeutic use EDAT- 2008/08/02 09:00 MHDA- 2009/03/11 09:00 CRDT- 2008/08/02 09:00 PHST- 2008/08/02 09:00 [pubmed] PHST- 2009/03/11 09:00 [medline] PHST- 2008/08/02 09:00 [entrez] AID - cgt200862 [pii] AID - 10.1038/cgt.2008.62 [doi] PST - ppublish SO - Cancer Gene Ther. 2009 Feb;16(2):149-60. doi: 10.1038/cgt.2008.62. Epub 2008 Aug 1.