Macrophage Delivered HSV1716 Is Active against Triple Negative Breast Cancer.

Autor: Kwan, Amy, Howard, Faith, Winder, Natalie, Atkinson, Emer, Jailani, Ameera, Patel, Priya B., Allen, Richard, Ottewell, Penelope D., Shaw, Gary C., Conner, Joe, Wilson, Caroline, Srivastava, Sanjay K., Danson, Sarah J., Lewis, Claire, Brown, Janet E., Muthana, Munitta
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Zdroj: Future Pharmacology; Dec2022, Vol. 2 Issue 4, p444-459, 16p
Abstrakt: Oncolytic viruses (OV) promote anti-tumour responses through the initiation of immunogenic cancer cell death which activates the host's systemic anti-tumour immunity. We have previously shown that intravenously administered HSV1716 is an effective treatment for mammary cancer. However, intravenous administration of a virus has the potential to result in neutralization and sequestration of the virus which may reduce efficacy. Here, we show that the oncolytic virus HSV1716 can be administered within a cellular carrier (macrophages). PyMT and 4T1 murine mammary cancer cell lines were implanted into immuno-competent murine models (orthotopic primary, early metastatic and brain metastasis models). HSV1716 or macrophages armed with HSV1716 (M-HSV1716) were administered intravenously, and tumour size was quantified using caliper measurement or bioluminescence imaging. Administration of M-HSV1716 led to tumour shrinkage and increased the survival of animals. Furthermore, these results were achieved with a 100-fold lower viral load, which has the potential for decreased toxicity. Our results demonstrate that M-HSV1716 is associated with activity against murine mammary cancers and provides an alternative platform for the systemic delivery of OV. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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