Format

Send to

Choose Destination
Mol Ther Oncolytics. 2017 Aug 9;6:90-99. doi: 10.1016/j.omto.2017.08.002. eCollection 2017 Sep 15.

Myxoma Virus Optimizes Cisplatin for the Treatment of Ovarian Cancer In Vitro and in a Syngeneic Murine Dissemination Model.

Author information

1
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR 72205-7199, USA.
2
The Center for Microbial Pathogenesis and Host Inflammatory Responses, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

Abstract

A therapeutic approach to improve treatment outcome of ovarian cancer (OC) in patients is urgently needed. Myxoma virus (MYXV) is a candidate oncolytic virus that infects to eliminate OC cells. We found that in vitro MYXV treatment enhances cisplatin or gemcitabine treatment by allowing lower doses than the corresponding IC50 calculated for primary OC cells. MYXV also affected OC patient ascites-associated CD14+ myeloid cells, one of the most abundant immunological components of the OC tumor environment; without causing cell death, MYXV infection reduces the ability of these cells to secrete cytokines such as IL-10 that are signatures of the immunosuppressive tumor environment. We found that pretreatment with replication-competent but not replication-defective MYXV-sensitized tumor cells to later cisplatin treatments to drastically improve survival in a murine syngeneic OC dissemination model. We thus conclude that infection with replication-competent MYXV before cisplatin treatment markedly enhances the therapeutic benefit of chemotherapy. Treatment with replication-competent MYXV followed by cisplatin potentiated splenocyte activation and IFNγ expression, possibly by T cells, when splenocytes from treated mice were stimulated with tumor cell antigen ex vivo. The impact on immune responses in the tumor environment may thus contribute to the enhanced antitumor activity of combinatorial MYXV-cisplatin treatment.

KEYWORDS:

M062R-null MYXV; MYXV; chemotherapy; immunotherapy; myxoma virus; oncolytic; ovarian cancer; synergism; syngeneic; virotherapy

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center