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  • 1
    Keywords: CANCER ; CELLS ; EXPRESSION ; radiotherapy ; tumor ; TUMOR-CELLS ; AGENTS ; CELL ; Germany ; LUNG ; MODEL ; MODELS ; THERAPY ; SYSTEM ; TUMORS ; MICE ; TRANSDUCTION ; INFECTION ; REDUCTION ; RAT ; antibodies ; antibody ; TARGET ; virus ; VECTOR ; metastases ; US ; TRANSFORMATION ; VACCINE ; IMMUNE-RESPONSE ; vaccination ; TARGETS ; TUMOR CELLS ; CANCER-THERAPY ; EFFECTOR ; AGENT ; ONCOLOGY ; PROGRAM ; CAPACITY ; parvovirus ; oncolysis ; INTERLEUKIN-12 ; IMMUNE-SYSTEM ; TUMOR-CELL ; ANIMAL-MODEL ; TRANSFORMED-CELLS ; tumor targeting ; animal ; animal model ; IMPROVEMENT ; anticancer agent ; ANTICANCER AGENTS ; HOLD ; OSTEOSARCOMA LUNG METASTASES
    Abstract: Oncolytic viruses have emerged as a novel class of potent anticancer agents offering an improvement on chemo-and radiotherapy in terms of tumor targeting and reduction of side-effects. Among these agents, autonomous parvoviruses have attracted the attention of researchers for their ability to preferentially replicate in and kill transformed cells, and to suppress tumors in the absence of adverse reactions in various animal models. We have previously shown that lethally irradiated autologous tumor cells can support parvovirus H-1PV production and serve as carriers to deliver progeny H-1PV into the vicinity of lung metastases in a rat tumor model, resulting in H-1PV infection of and multiplication in metastatic cells. It is known that irradiated autologous (neoplastic) cells can also act as a therapeutic vaccine against the original tumor. Yet the ability of these cells to suppress metastases in the above model was found to be much increased as a result of their H-1PV infection. This prompted us to determine whether H-1PV boosted the tumor-suppressing capacity of the autologous vaccine by increasing its immunogenic potential and/or by making it a factory of oncolytic vi. ruses able to reach and destroy the metastases. Both effects could be dissociated in the presence of neutralising antibodies which either prevent the progeny viruses from spreading to metastatic cells, or deplete the CD8 effector cells from the immune system. This strategy revealed that the H-1PV infection of tumor cells enhanced their ability to trigger an immune response for which uninfected tumor cells could be the targets. thereby amplifying and taking over from the direct viral oncolytic activity. This dual oncolytic/vaccinal effect of H-1PV holds out promises of clinical applications to cancer therapy
    Type of Publication: Journal article published
    PubMed ID: 17487410
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  • 2
    Keywords: CELLS ; EXPRESSION ; CELL ; Germany ; human ; THERAPY ; EXPOSURE ; LONG-TERM ; GENE ; GENE-EXPRESSION ; gene therapy ; TRANSDUCTION ; gene transfer ; GENE-TRANSFER ; MARKER ; BIOLOGY ; TARGET ; virus ; DELETION ; VECTOR ; PROMOTER ; NUMBER ; PROMOTERS ; genetics ; EFFICIENT ; REPLICATION ; GENE-THERAPY ; RETROVIRAL VECTORS ; CONSTRUCTION ; heredity ; FELINE FOAMY VIRUS ; ARRAY ; TERMINAL GAG DOMAIN ; PROFILES ; ENV LEADER PROTEIN ; UBIQUITIN ; RETROVIRUS ; ACCESSORY BET PROTEIN ; biosafety ; deficient vector ; lacZ ; NOD/SCID-REPOPULATING CELLS ; SIN vector ; UBIQUITIN-C
    Abstract: As serious side effects affected recent virus-mediated gene transfer studies, novel vectors with improved safety profiles are urgently needed. In the present study, replication-deficient retroviral vectors based on feline foamy virus (FFV) were constructed and analyzed. The novel FFV vectors are devoid of almost the complete env gene plus the internal promoter - accessory bel gene cassette including the gene for the viral transcriptional transactivator Bel1/Tas. In these Bel1/Tas-independent vectors, expression of the lacZ (beta-galactosidase) marker gene is directed by the heterologous, constitutively active human ubiquitin C promoter (ubl). Env-transcomplemented vectors have unconcentrated titers of more than 10(5) transducing units/ml. The vectors allow efficient transduction of a broad array of diverse target cells, which can be increased by repeated vector exposure. However, the number of lacZ marker gene expressing cells decreased slightly upon serial passages of the transduced cells. Vectors carrying a self-inactivating (SIN) deletion of the TATA box and most parts of the viral promoter were not rescued by wt FFV whereas those with the intact or a partially deleted promoter were readily reactivated. This finding indicates that the viral promoters are in fact non-functional, pointing to a highly advantageous safety profile of these new FFV-ubi-lacZ-SIN vectors
    Type of Publication: Journal article published
    PubMed ID: 17203107
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