Treatment of an Alveolar Rhabdomyosarcoma Allograft with Recombinant Myxoma Virus and Oclacitinib

Abstract

Purpose

Rhabdomyosarcomas (RMS) are difficult tumors to treat with conventional therapies. Publications indicate that oncolytic virotherapy (OV) could benefit cancer patients with tumors that are refractory to conventional treatments. It is believed that the efficacy of OV can be enhanced when used in combination with other treatments. This study evaluated the response of mice with aggressive alveolar RMS (ARMS) allografts to treatment with an OV [recombinant myxoma virus (MYXVΔserp2)] in combination with a Janus kinase (JAK) inhibitor (oclacitinib). Oclacitinib is known to inhibit JAK1 and JAK2 cell signaling pathways, which should limit the antiviral Type I interferon response. However, oclacitinib does not inhibit immune pathways that promote antigen presentation, which help stimulate an anti-cancer immune response.

Materials and Methods

To determine if MYXVΔserp2 and oclacitinib could improve outcomes in animals with ARMS, nude mice were inoculated subcutaneously with murine ARMS cells to establish tumors. Immune responses, tumor growth, and clinical signs in mice treated with combination therapy were compared to mice given placebo therapy and mice treated with OV alone.

Results

Combination therapy was safe; no viral DNA was detected in off-target organs, only within tumors. As predicted, viral DNA was detected in tumors of mice given oclacitinib and MYXVΔserp2 for a longer time period than mice treated with OV alone. Although tumor growth rates and median survival times were not significantly different between groups, clinical signs were less severe in mice treated with OV.

Conclusion

Our data indicate that MYXVΔserp2 treatment benefits mice with ARMS by reducing clinical signs of disease and improving quality of life.

Keywords:

• oncolytic virus
• poxvirus
• Janus kinase inhibitor
• sarcoma

Acknowledgments

The Elsa U Pardee Foundation generously funded this study. We thank the undergraduate (Mikaela Maldonado, Garin Wilson) and veterinary (Kayla Gravelle) students who helped with daily evaluation of the mice.

Disclosure

Ms Barbara Graham reports grants from The Elsa U Pardee Foundation, during the conduct of the study. The authors report no conflicts of interest in this work.