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Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses
Open accessAbstract
Clinical trials are testing oncolytic viruses (OVs) as therapies for cancer. We have shown that animals that have brain tumors and are treated with a herpes simplex virus (HSV)-derived OV live significantly longer when cyclophosphamide (CPA) is preadministered. Here, we explore the mechanisms behind this finding. In a syngeneic rat glioma model, intratumoral HSV administration is associated with rapid increase of natural killer cells, microglia/macrophages (CD68+and CD163+), and IFN-γ. Pretreatment with CPA enhances HSV replication and oncolysis and reduces an HSV-mediated increase in CD68+and CD163+cells and intratumoral IFN-γ. Molecular imaging shows CPA pretreatment to inhibit HSV-induced infiltration of tumor-associated phagocytic cells. Our results reveal molecular and cellular mechanisms that inhibit intratumoral spread of HSV and suggest a therapeutic path for improving the efficacy of virotherapy as a treatment for cancer.
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Cited by
Oncolytic viruses: a new class of immunotherapy drugs
Kaufman, H. L., Kohlhapp, F. J., & Zloza, A. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4663 · Cited by 1,642
Markert, J. M., Liechty, P. G., Wang, W., Gaston, S., Braz, E., Karrasch, M., Nabors, L. B., Markiewicz, M., Lakeman, A. D., Palmer, C. A., et al. (2009) · Molecular Therapy · doi:10.1038/mt.2008.228 · Cited by 401
Oncolytic Viruses and the Immune System: The Dynamic Duo
Lemos de Matos, A., Franco, L. S., & McFadden, G. (2020) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2020.01.001 · Cited by 269
Oncolytic HSV-1 Infection of Tumors Induces Angiogenesis and Upregulates CYR61
Kurozumi, K., Hardcastle, J., Thakur, R., Shroll, J., Nowicki, M., Otsuki, A., Chiocca, E. A., & Kaur, B. (2008) · Molecular Therapy · doi:10.1038/mt.2008.112 · Cited by 86
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Metadata
- Authors
- Fulci, G., Breymann, L., Gianni, D., Kurozomi, K., Rhee, S. S., Yu, J., Kaur, B., Louis, D. N., Weissleder, R., Caligiuri, M. A., & Chiocca, E. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2006-08-22
- Volume
- 103
- Issue
- 34
- Pages
- 12873-12878
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2065360869
- Cited by
- 357
- References
- 0
- FWCI
- 14.84
- Type
- journal article
- Language
- en
- Open access
- green
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- Fulci, G., Breymann, L., Gianni, D., Kurozomi, K., Rhee, S. S., Yu, J., Kaur, B., Louis, D. N., Weissleder, R., Caligiuri, M. A., & Chiocca, E. A. (2006). Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0605496103
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