 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Dec 26, 2007 |
| Title |
Eradication of Solid Human Tumors in Nude Mice with an Intravenously Injected Light-Emitting Oncolytic Vaccinia Virus |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Previously we reported that a recombinant vaccinia virus (VACV) carrying a light-emitting fusion gene enters, replicates in, and reveals the locations of tumors in mice. A new recombinant VACV, GLV-1h68, as a simultaneous diagnostic and therapeutic agent, was constructed by inserting three expression cassettes (encoding Renilla luciferase-green fluorescent protein (RUC-GFP) fusion, b-galactosidase, and b-glucuronidase) into the F14.5L, J2R (encoding thymidine kinase, TK), and A56R (encoding hemagglutinin, HA) loci of the viral genome, respectively. Intravenous (i.v.) injections of GLV-1h68 (1 × 107 pfu/mouse) into nude mice with established (500 mm3) subcutaneous (s.c.) GI-101A human breast tumors were used to evaluate its toxicity, tumor targeting specificity and oncolytic efficacy. GLV-1h68 demonstrated an enhanced tumor targeting specificity and much reduced toxicity compared to its parental LIVP strains. The tumors colonized by GLV-1h68 exhibited growth, inhibition, and regression phases followed by tumor eradication within 130 days in 95% of the mice tested. Tumor regression in live animals was monitored in real time based on decreasing light emission, hence demonstrating the concept of a combined oncolytic virus-mediated tumor diagnosis and therapy system. Transcriptional profiling of regressing tumors based on a mouse-specific platform revealed gene expression signatures consistent with immune defense activation, inclusive of interferon stimulated genes (STAT-1 and IRF-7), cytokines, chemokines and innate immune effector function. These findings suggest that immune activation may combine with viral oncolysis to induce tumor eradication in this model, providing a novel perspective for the design of oncolytic viral therapies for human cancers.
Objective: To determine the gene expression changes induced by GLV-1h68 vaccinia virus injection in mouse carrying human breast cancer implant and leading to tumor eradication.
Methods: Gene expression was analyzed using oligonucleotide microarrays. Responsiveness to vaccina virus injection was assessed by toxicity and survival study, gene expression anaysis and tumor volume change.
Result: The tumors colonized by GLV-1h68 exhibited growth, inhibition, and regression phases followed by tumor eradication within 130 days in 95% of the mice tested. Tumor regression in live animals was monitored in real time based on decreasing light emission, hence demonstrating the concept of a combined oncolytic virus-mediated tumor diagnosis and therapy system. Transcriptional profiling of regressing tumors based on a mouse-specific platform revealed gene expression signatures consistent with immune defense activation, inclusive of interferon stimulated genes (STAT-1 and IRF-7), cytokines, chemokines and innate immune effector function.
Conclusion: Our findings suggest that immune activation may combine with viral oncolysis to induce tumor eradication in this model, providing a novel perspective for the design of oncolytic viral therapies for human cancers.
Keywords: Responsiveness to vaccina virus injection
|
| |
|
| Overall design |
tumor tissues 3 and 6 weeks post virus injection
|
| |
|
| Citation(s) |
17942938 |
| |
| Submission date |
Jul 18, 2007 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Francesco Maria Marincola |
| E-mail(s) |
fmarincola@sidra.org
|
| Phone |
301-793-8210
|
| Organization name |
Sidra Medical and Research Center
|
| Street address |
Al Nasr Tower, AL Corniche Street, PO Box 26999
|
| City |
Doha |
| ZIP/Postal code |
PO Box 26999 |
| Country |
Qatar |
| |
|
| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
|
| Samples (10)
|
| GSM211436 |
tumor tissue 3 weeks post virus injection mouse 1 |
| GSM211437 |
tumor tissue 3 weeks post virus injection mouse 2 |
| GSM211438 |
tumor tissue 3 weeks post virus injection mouse 3 |
| GSM211439 |
tumor tissue 3 weeks post virus injection mouse 4 |
| GSM211440 |
tumor tissue 3 week control (mixed sample from 4 mice) |
| GSM211441 |
tumor tissue 6 weeks post virus injection mouse 1 |
| GSM211442 |
tumor tissue 6 weeks post virus injection mouse 2 |
| GSM211443 |
tumor tissue 6 weeks post virus injection mouse 3 |
| GSM211444 |
tumor tissue 6 weeks post virus injection mouse4 |
| GSM211445 |
tumor tissue 6 week control (mixed sample from 4 mice) |
|
| Relations |
| BioProject |
PRJNA101631 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE8513_RAW.tar |
32.5 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...