Recombinant Parvoviruses Armed to Deliver CXCL4L1 and CXCL10 Are Impaired in Their Antiangiogenic and Antitumoral Effects in a Kaposi Sarcoma Tumor Model Due To the Chemokines' Interference with the Virus Cycle
| Autor: | Isabelle Ronsse, Katrien Van Raemdonck, Christiane Dinsart, Alexandra Stroh-Dege, Muriel Lavie, Sofie Struyf, Jo Van Damme, Jean Rommelaere, Kalliopi Pervolaraki |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Chemokine Genetic Vectors Mice Nude Angiogenesis Inhibitors Antineoplastic Agents CXCR3 Platelet Factor 4 Virus Parvovirus 03 medical and health sciences Mice Genetics CXCL10 Cytotoxic T cell Animals Humans Molecular Biology Sarcoma Kaposi Mice Inbred BALB C biology virus diseases Genetic Therapy biology.organism_classification Virology Oncolytic virus Chemokine CXCL10 Disease Models Animal 030104 developmental biology Cell culture Cancer research biology.protein Molecular Medicine Female |
| Zdroj: | Human gene therapy. 28(3) |
| ISSN: | 1557-7422 |
| Popis: | Application of oncolytic viruses is a valuable option to broaden the armament of anticancer therapies, as these combine specific cytotoxic effects and immune-stimulating properties. The self-replicating H-1 parvovirus (H-1PV) is a prototypical oncolytic virus that, besides targeting tumor cells, also infects endothelial cells, thus combining oncolytic and angiostatic traits. To increase its therapeutic value, H-1PV can be armed with cytokines or chemokines to enhance the immunological response. Some chemokines-more specifically, the CXCR3 ligands CXCL4L1 and CXCL10-combine immune-stimulating properties with angiostatic activity. This study explores the therapeutic value of recombinant parvoviruses carrying CXCL4L1 or CXCL10 transgenes (Chi-H1/CXCL4L1 or Chi-H1/CXCL10, respectively) to inhibit the growth of the human Kaposi sarcoma cell line KS-IMM. KS-IMM cells infected by Chi-H1/CXCL4L1 or Chi-H1/CXCL10 released the corresponding chemokine and showed reduced migratory capacity. Therefore, the antitumoral capacity of Chi-H1/CXCL4L1 or Chi-H1/CXCL10 was tested in mice. Either in vitro infected KS-IMM cells were injected or subcutaneously growing KS-IMM xenografts were treated by peritumoral injections of the different viruses. Surprisingly, the transgenes did not increase the antitumoral effect of natural H-1PV. Further experiments indicated that CXCL4L1 and CXCL10 interfered with the expression of the viral NS1 protein in KS-IMM cells. These results indicate that the outcome of parvovirus-based delivery of CXCR3 ligands might be tumor cell type dependent, and hence its application must be considered carefully. |
| Databáze: | OpenAIRE |
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