Active specific immunotherapy for lethal canine hemangiosarcoma: A model system for the treatment of angiosarcoma with curative intent
| Autor: | Heidi Hottinger, Matthew M. Halpert, Nicola Wilson, Caleb Hudson, Oscar Ramirez, Zharkyn Omarbekov, Lori Seelhoff, William K. Decker, Yunyu Chen, Laurel Douglass, Ratan D. Bhardwaj, Sindy Piscoya, Vanaja Konduri, Brittany Neal, Qizhi Cathy Yao, Dan Liang, Shonda Stallings, Vinod Ravi, Jonathan M. Levitt, Lisa DiBernardi |
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| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 35:e14539-e14539 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2017.35.15_suppl.e14539 |
| Popis: | e14539 Background: Angiosarcoma is a deadly malignant neoplasm of the vascular endothelium. Metastases are often present at diagnosis, and 5-year survival is only 10-30%. Though it comprises only 1% all soft tissue sarcoma diagnoses, it is a major killer among companion canines, responsible for an estimated 120,000 deaths per year in the US. The canine disease (termed HSA) closely mimics the human disease in both pathology and genetics. It frequently presents in the dog as acute hemoabdomen secondary to splenic rupture. Even if life-saving splenectomy is performed, median OS is only 48 days, and 1 year OS hovers at 0%. Given the accelerated timeline of the canine disease, the outbred dog is an ideal system in which to translate novel therapeutic approaches. Here we report an analysis of a phase I multi-site, open-label veterinary trial of chemo-immunotherapy performed on consecutively-presenting splenectomized companion canines with histopathologically-verified HSA. Methods: Subjects were administered two cycles of 20 mg/m2 (low-dose) doxorubicinand an autologous cell-therapy reported to generate durable CD8+ memory similar to that of physiologic viral infection. Vaccine was generated from mobilized peripheral blood and cryopreserved tumor antigen and was administered with type I interferon. Disease burden was monitored monthly by abdominal ultrasound, chest x-ray, and echocardiogram. Results: At the time of submission, median OS had not been reached in the per protocol population, with 75% of animals alive and healthy (NED or ongoing PR) at up to 1 year post-splenectomy (p < 0.0002). Ultrasound documented resolution of local mesenteric disease in one animal, sternal lymphadenopathy in another, and hepatic metastases in a third. In the intent-to-treat population, median OS was 109 days with 43% of animals alive and healthy at up to 1 year post-splenectomy. Conclusions: Administration of autologous cell therapy with low-dose doxorubicin is feasible, safe, and highly efficacious in the companion canines. If subjects survived long enough to begin treatment, prognosis became favorable. The results suggest that additional clinical studies in both canines and humans are warranted. |
| Databáze: | OpenAIRE |
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