Persistence of Infectious Canine Distemper Virus in Murine Xenotransplants of Canine Histiocytic Sarcoma Cells after Intratumoral Application.

Oncolytic viruses and morbilliviruses in particular, represent an interesting therapeutic approach for tumors with a poor prognosis and frequent resistance to conventional therapies. Canine histiocytic sarcomas (HS) exemplify such a neoplasm in need for new curative approaches. Previous investigations demonstrated a limited success of an acute intratumoral application of canine distemper virus (CDV) on xenotransplanted canine histiocytic sarcoma cells (DH82 cells), while persistently CDV-infected DH82 cell transplants exhibited a complete spontaneous regression. Therefore, the present study focuses on an intratumoral application of persistently CDV vaccine strain Onderstepoort-infected DH82 (DH82 Ond p.i.) cells into non-infected subcutaneous DH82 cell transplants in a murine model. DH82 cell transplants that received 10 applications, two days apart, showed a transient growth retardation as well as larger areas of intratumoral necrosis, lower mitotic rates, and a decreased intratumoral vascularization compared to controls. Viral mRNA was detected in all neoplasms following application of DH82 Ond p.i. cells until 66 days after the last injection. Furthermore, infectious virus was present until 62 days after the last injection. Although complete regression was not achieved, the present application regimen provides promising results as a basis for further treatments, particularly with genetically modified viruses, to enhance the observed effects.

[Eccrine adenoma in a cat]. / Adenom der ekkrinen Drüsen bei einer Katze.

Tumors originating from eccrine glands are rare findings in dogs and cats. In most cases, the tumors are malignant, while adenomas are only reported anecdotally. In the present case, a one-year-old female, spayed cat was presented with a swelling of the footpad of the right forelimb. Initially, the mass possessed a diameter of 2 cm which progressed to 4 cm within the following two months. At the latter time point the tumor was ulcerated. After surgical removal, histological and immunohistochemical analyses were performed. Histologically, a well demarcated, nodular, multilobular mass was present. The cuboidal to columnar neoplastic cells were arranged in tubular and acinar structures. Tumor cells possessed large, round to oval nuclei with moderately distinct nucleoli. Mitotic figures averaged 0-1 per high power field. Additionally, large areas of chondroid metaplasia were evident. Immunohistochemically, neoplastic cells were positive for pan-cytokeratin AE1/AE3 whereas thyroid transcription factor 1 (TTF1) was not expressed. Based on the histological and immunohistochemical findings an adenoma of the eccrine glands was diagnosed.

Intratumoral Canine Distemper Virus Infection Inhibits Tumor Growth by Modulation of the Tumor Microenvironment in a Murine Xenograft Model of Canine Histiocytic Sarcoma.

Histiocytic sarcomas refer to highly aggressive tumors with a poor prognosis that respond poorly to conventional treatment approaches. Oncolytic viruses, which have gained significant traction as a cancer therapy in recent decades, represent a promising option for treating histiocytic sarcomas through their replication and/or by modulating the tumor microenvironment. The live attenuated canine distemper virus (CDV) vaccine strain Onderstepoort represents an attractive candidate for oncolytic viral therapy. In the present study, oncolytic virotherapy with CDV was used to investigate the impact of this virus infection on tumor cell growth through direct oncolytic effects or by virus-mediated modulation of the tumor microenvironment with special emphasis on angiogenesis, expression of selected MMPs and TIMP-1 and tumor-associated macrophages in a murine xenograft model of canine histiocytic sarcoma. Treatment of mice with xenotransplanted canine histiocytic sarcomas using CDV induced overt retardation in tumor progression accompanied by necrosis of neoplastic cells, increased numbers of intratumoral macrophages, reduced angiogenesis and modulation of the expression of MMPs and TIMP-1. The present data suggest that CDV inhibits tumor growth in a multifactorial way, including direct cell lysis and reduction of angiogenesis and modulation of MMPs and their inhibitor TIMP-1, providing further support for the concept of its role in oncolytic therapies.