Читать книгу Veterinary Surgical Oncology - Группа авторов - Страница 148

The expression of genes encoding for immunostimulatory cytokines or tumor‐associated antigens that may negatively influence tumor viability is being used more frequently. Several attenuated poxvirus vector systems have been developed, for example, NYVAC (Copenhagen vaccinia virus), TROVAC (Fowl pox virus), and ALVAC (Canary pox virus) viral vectors (Paoletti et al. 1995). These recombinant viruses have been administered without any major side effects to animals and humans (Fries et al. 1996). To prevent the recurrence of FSA, ALVAC‐ or NYVAC‐based recombinants expressing feline or human IL2, respectively, were administered to domestic cats. In the absence of immunotherapy, recurrence was observed in 61% of animals within a 12‐month follow‐up period after treatment with surgery and iridium‐based radiotherapy. Only 39% of the cats receiving NYVAC‐human interleukin‐2 (IL‐2) and 28% of the cats receiving ALVAC‐feline IL‐2 exhibited tumor recurrences (Jourdier et al. 2003). Additionally, intratumoral administration of histoincompatible cells expressing human IL‐2 in spontaneous canine melanoma and feline FSA, in combination with surgery and radiotherapy, has been shown to increase the disease‐free period and survival time (Quintin‐Colonna et al. 1996). Haagsman et al. (2013) reported no effect of local interleukin‐2 therapy on canine PNSTs after marginal surgical excision in a double‐blind randomized placebo‐controlled study.

Angiogenesis plays an essential role in tumor growth, invasion, and metastasis. Vascular endothelial cell growth factor (VEGF) is one of the key growth factors regulating the process of angiogenesis. In a study of De Queiroz et al. (2013), serum VEGF was measured by enzyme‐linked immunosorbent assay quantitative method. Dogs with hemangiopericytoma showed higher serum VEGF levels compared to the patients with malignant PNSTs. Serum VEGF decreases after sarcoma resection. Serum VEGF and neutrophil counts are positively correlated, and negative between VEGF and hemoglobin content in dogs with sarcoma (De Quieroz et al. 2013). Kamstock et al. (2007) evaluated the effect of xenogeneic VEGF vaccination in dogs with cutaneous STS. A total of six immunizations with a human VEGF vaccine were administered intradermally to dogs once every other week for three immunizations, then once every four weeks for three additional immunizations. Eventually, four out of nine dogs remained long enough in the study to receive five or more immunizations. The five dogs that failed to receive greater than three immunizations were removed from the study due to progressive tumor growth. A decrease in plasma VEGF concentration was observed in three of the four dogs that received five or more VEGF immunizations. Tumor microvessel density (MVD) was evaluated in biopsy specimens on weeks 6 and 16 of the study from these four dogs. Two of the four multiply vaccinated dogs demonstrated a significant (>50%) decrease in tumor MVD at one or more time points. It should be noted that in one of these dogs, tumor MVD increased at a later time point coincident with progressive growth. In the other two dogs, tumor MVD remained relatively constant after immunization of the tumor. Based on these results, it appeared that repeated VEGF immunization was capable of inhibiting tumor angiogenesis in at least half of the dogs.