Preclinical Evaluation of Oncolytic Δγ134.5 Herpes Simplex Virus Expressing Interleukin-12 for Therapy of Breast Cancer Brain Metastases
The metastasis of breast cancer to the brain and central nervous system (CNS) is a problem of increasing importance. As improving treatments continue to extend patient survival, the incidence of CNS metastases from breast cancer is on the rise. New treatments are needed, as current treatments are li...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | International Journal of Breast Cancer |
| Online Access: | http://dx.doi.org/10.1155/2012/628697 |
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| author | James J. Cody Pietro Scaturro Alan B. Cantor G. Yancey Gillespie Jacqueline N. Parker James M. Markert |
| author_facet | James J. Cody Pietro Scaturro Alan B. Cantor G. Yancey Gillespie Jacqueline N. Parker James M. Markert |
| author_sort | James J. Cody |
| collection | DOAJ |
| description | The metastasis of breast cancer to the brain and central nervous system (CNS) is a problem of increasing importance. As improving treatments continue to extend patient survival, the incidence of CNS metastases from breast cancer is on the rise. New treatments are needed, as current treatments are limited by deleterious side effects and are generally palliative. We have previously described an oncolytic herpes simplex virus (HSV), designated M002, which lacks both copies of the γ134.5 neurovirulence gene and carries a murine interleukin 12 (IL-12) expression cassette, and have validated its antitumor efficacy in a variety of preclinical models of primary brain tumors. However, M002 has not been yet evaluated for use against metastatic brain tumors. Here, we demonstrate the following: both human breast cancer and murine mammary carcinoma cells support viral replication and IL-12 expression from M002; M002 replicates in and destroys breast cancer cells from a variety of histological subtypes, including “triple-negative” and HER2 overexpressing; M002 improves survival in an immunocompetent model more effectively than does a non-cytokine control virus. Thus, we conclude from this proof-of-principle study that a γ134.5-deleted IL-12 expressing oncolytic HSV may be a potential new therapy for breast cancer brain metastases. |
| format | Article |
| id | doaj-art-5d93728589f043159e50b6a7d373b5ac |
| institution | Kabale University |
| issn | 2090-3170 2090-3189 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Breast Cancer |
| spelling | doaj-art-5d93728589f043159e50b6a7d373b5ac2025-02-03T01:09:37ZengWileyInternational Journal of Breast Cancer2090-31702090-31892012-01-01201210.1155/2012/628697628697Preclinical Evaluation of Oncolytic Δγ134.5 Herpes Simplex Virus Expressing Interleukin-12 for Therapy of Breast Cancer Brain MetastasesJames J. Cody0Pietro Scaturro1Alan B. Cantor2G. Yancey Gillespie3Jacqueline N. Parker4James M. Markert5Division of Infectious Diseases, Department of Pediatrics, The University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL 35294, USADivision of Neurosurgery, Department of Surgery, The University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL 35294, USADivision of Preventive Medicine, Department of Medicine, The University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL 35294, USADivision of Neurosurgery, Department of Surgery, The University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL 35294, USADivision of Infectious Diseases, Department of Pediatrics, The University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL 35294, USADivision of Infectious Diseases, Department of Pediatrics, The University of Alabama at Birmingham, 1720 2nd Avenue South, Birmingham, AL 35294, USAThe metastasis of breast cancer to the brain and central nervous system (CNS) is a problem of increasing importance. As improving treatments continue to extend patient survival, the incidence of CNS metastases from breast cancer is on the rise. New treatments are needed, as current treatments are limited by deleterious side effects and are generally palliative. We have previously described an oncolytic herpes simplex virus (HSV), designated M002, which lacks both copies of the γ134.5 neurovirulence gene and carries a murine interleukin 12 (IL-12) expression cassette, and have validated its antitumor efficacy in a variety of preclinical models of primary brain tumors. However, M002 has not been yet evaluated for use against metastatic brain tumors. Here, we demonstrate the following: both human breast cancer and murine mammary carcinoma cells support viral replication and IL-12 expression from M002; M002 replicates in and destroys breast cancer cells from a variety of histological subtypes, including “triple-negative” and HER2 overexpressing; M002 improves survival in an immunocompetent model more effectively than does a non-cytokine control virus. Thus, we conclude from this proof-of-principle study that a γ134.5-deleted IL-12 expressing oncolytic HSV may be a potential new therapy for breast cancer brain metastases.http://dx.doi.org/10.1155/2012/628697 |
| spellingShingle | James J. Cody Pietro Scaturro Alan B. Cantor G. Yancey Gillespie Jacqueline N. Parker James M. Markert Preclinical Evaluation of Oncolytic Δγ134.5 Herpes Simplex Virus Expressing Interleukin-12 for Therapy of Breast Cancer Brain Metastases International Journal of Breast Cancer |
| title | Preclinical Evaluation of Oncolytic Δγ134.5 Herpes Simplex Virus Expressing Interleukin-12 for Therapy of Breast Cancer Brain Metastases |
| title_full | Preclinical Evaluation of Oncolytic Δγ134.5 Herpes Simplex Virus Expressing Interleukin-12 for Therapy of Breast Cancer Brain Metastases |
| title_fullStr | Preclinical Evaluation of Oncolytic Δγ134.5 Herpes Simplex Virus Expressing Interleukin-12 for Therapy of Breast Cancer Brain Metastases |
| title_full_unstemmed | Preclinical Evaluation of Oncolytic Δγ134.5 Herpes Simplex Virus Expressing Interleukin-12 for Therapy of Breast Cancer Brain Metastases |
| title_short | Preclinical Evaluation of Oncolytic Δγ134.5 Herpes Simplex Virus Expressing Interleukin-12 for Therapy of Breast Cancer Brain Metastases |
| title_sort | preclinical evaluation of oncolytic δγ134 5 herpes simplex virus expressing interleukin 12 for therapy of breast cancer brain metastases |
| url | http://dx.doi.org/10.1155/2012/628697 |
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