Vaccination with doxorubicin for treating dog hemangiosarcoma

Abstract

Angiosarcomas are highly aggressive soft tissue tumors with poor prognosis in both humans and dogs. In dogs, visceral hemangiosarcoma offers a relevant spontaneous model for evaluating novel therapies. Surgery alone yields a median survival of 1-3 months, and treatment with doxorubicin (DOX), alone or in combination (e.g., with propranolol), modestly extends median survival time to 5-7 months, with a 1-year survival of around 10%. We developed a conjugate vaccine technology, called immune Boost (iBoost), and hypothesized that combining DOX with an iBoost vaccine targeting extracellular vimentin (eVim) could improve survival without added toxicity. Twenty-three dogs with visceral hemangiosarcoma received six cycles of DOX every two weeks post-splenectomy, alongside four doses every other week of eVim iBoost immunotherapy, followed by maintenance vaccinations every two months. Outcomes were compared to historical controls treated with DOX alone. Compared to the control group the median overall survival time increased from 136 to 235 days (NS), restricted mean survival time at one year increased with 81 days (= 0.02) and 1-year survival rate was 44% versus 14% (= 0.0344). The combination was well-tolerated, with no systemic vaccine-related toxicity. Adding dog eVim vaccine to DOX appears to improve survival without added toxicity in dogs with hemangiosarcoma. These results support further clinical development, including evaluation in human angiosarcoma.