The use of oncolytic viruses is an innovative approach to lyse tumor cells and induce antitumor immune responses. Eight dogs diagnosed with carcinoma/adenocarcinoma were intratumorally treated with ICOCAV15, an oncolytic canine adenovirus (CAV). To evaluate the treatment’s safety, a blood count, biochemistry, and coagulation test were performed before treatment and during follow-up. Immune populations were analyzed by flow cytometry. Anti-adenovirus antibodies were also determined. The immune infiltration, vascularization, and viral presence in the tumor were determined by CD3, CD4, CD20, CD31 and CAV by immunohistochemistry. All the dogs maintained a good quality of life during follow-up, and some had increased median survival time when compared with dogs treated with chemotherapy. No treatment-related adverse effects were detected. The Response Evaluation Criteria In Solid Tumors criteria were also assessed: two patients showed a partial response and the rest showed stable disease at various times during the study. ICOCAV15 was detected inside the tumor during follow-up, and antiviral antibodies were detected in all patients. Furthermore, the tumor-infiltrating immune cells increased after viral administration. Therefore, we suggest that intratumorally administered ICOCAV15 could represent as a new tool for the treatment of canine carcinoma because it is safe, well-tolerated by dogs, and shows promising results.
COVID-19 is a zoonotic disease caused by SARS-CoV-2. Infections of animals with SARS-CoV-2 have recently been reported, and an increase of severe lung pathologies in domestic dogs has also been detected by veterinarians in Spain. Therefore, further descriptions of the pathological processes in those animals that show symptoms similar to those described in humans affected by COVID-19 would be highly valuable. The potential for companion animals to contribute to the continued transmission and community spread of this known human-to-human disease is an urgent issue to be considered. Forty animals with pulmonary pathologies were studied by chest X-ray, ultrasound analysis, and computed tomography. Nasopharyngeal and rectal swabs were analyzed to detect canine pathogens, including SARS-CoV-2. An additional twenty healthy dogs living in SARS-CoV-2-positive households were included. Immunoglobulin detection by several immunoassays was performed. Our findings show that sick dogs presented severe alveolar or interstitial patterns with pulmonary opacity, parenchymal abnormalities, and bilateral lesions. The forty sick dogs were negative for SARS-CoV-2 but Mycoplasma spp. was detected in 26 of 33 dogs. Five healthy and one pathological dog presented IgG against SARS-CoV-2. Here we report that despite detecting dogs with α-SARS-CoV-2 IgG, we never obtained a positive RT-qPCR for SARS-SoV-2, not even in dogs with severe pulmonary disease; suggesting that even in the case of canine infection, transmission would be unlikely. Moreover, dogs living in COVID-19-positive households could have been more highly exposed to infection with SARS-CoV-2.
Intracranial hemangiomas are rare neoplastic lesions in dogs that usually appear with life-threatening symptoms. The treatment of choice is tumor resection; however, complete resection is rarely achieved. The patient’s prognosis therefore usually worsens due to tumor progression, and adjuvant treatments are required to control the disease. Oncolytic viruses are an innovative approach that lyses the tumor cells and induces immune responses. Here, we report the intratumoral inoculation of ICOCAV15 (an oncolytic adenovirus) in a canine intracranial hemangioma, as adjuvant treatment for incomplete tumor resection. The canine patient showed no side effects, and the tumor volume decreased over the 12 months after the treatment, as measured by magnetic resonance imaging using volumetric criteria. When progressive disease was detected at month 18, a new dose of ICOCAV15 was administered. The patient died 31.9 months after the first inoculation of the oncolytic adenovirus. Furthermore, tumor-infiltrated immune cells increased in number after the viral administrations, suggesting tumor microenvironment activation. The increased number of infiltrated immune cells, the long survival time and the absence of side effects suggest that ICOCAV15 could be a safe and effective treatment and should be further explored as a novel therapy for canine hemangiomas.
19 September 2023 in Veterinary Medicine and Science
Background: Vitamin D is essential for skeletal health, calcium homeostasis and general health. The major and more stable form of vitamin D in circulation is 25‐hydroxyvitamin D (25‐OH‐D); this is the most valuable indicator of vitamin D status. There are studies on laboratory and zoo‐housed chimpanzees; however, serum vitamin D status has not been documented in chimpanzees in range countries.Objectives: (1) Determine the range of circulating 25‐OH‐D concentrations in chimpanzees in range countries. (2) Assess the influence of age, sex, and sun exposure on 25‐OH‐D serum concentrations.Methods: Opportunistic blood samples were obtained from 127 clinically healthy chimpanzees. Serum 25‐OH‐D concentration was measured with a commercially available competitive ELISA.Results: The median overall 25‐OH‐D concentration for chimpanzees in range countries was 46.24 nmol/L (range: 17.10–109.23 nmol/L). Males had a significantly lower concentration (40.15 nmol/L) than females (49.61 nmol/L), and infants (37.99 nmol/L) had a significantly lower concentration than adults (46.04 nmol/L). Concentrations of 25‐OH‐D in chimpanzees in sunnier habitats were significantly higher compared to thick tropical forest habitat.Conclusion: The present constitutes a large dataset of serum 25‐OH‐D concentrations in range country sanctuary chimpanzees and contributes to document normal ranges. Age, sex, and sun exposure influenced serum concentrations of 25‐OH‐D in sanctuary chimpanzees.
Intravenous administration of oncolytic adenovirus (OAds) can be challenging, although various vehicles for the delivery of the virus to the tumor have been described. The efficacy of mesenchymal stem cells (MSCs) as a virus vehicle has been reported in mouse models and canine and human patients, but the actual action mechanism has never been described in patients. It is of importance to determine whether MSCs infected with OAds can reach the tumor and release the virus in a clinical setting. For this purpose, GFP-labeled MSCs were infected with an OAd and inoculated into a companion dog diagnosed with spontaneous lung carcinoma. Forty-eight hours later, the tumor was excised and analyzed microscopically by flow cytometry for GFP fluorescence detection, and a cellular culture was established. Peripheral blood samples were taken to quantify the oncolytic adenovirus by qRT-PCR. Green fluorescence cells detected in the cellular culture by microscopy and flow cytometry revealed 0.69% GFP-positive cells in the tumor. OAd in peripheral blood was confirmed by qRT-PCR during follow-up. For the first time, the tumoral-homing capacity of OAds infected-MSC has been confirmed in a clinical setting, helping to explain the clinical response mechanism, whose efficacy was previously reported in canine and human patients.
1 January 2024 in Transboundary and Emerging Diseases
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was identified as the causal agent behind coronavirus disease 2019 (COVID‐19), a disease declared pandemic in 2020. Because of the zoonotic origin of SARS‐CoV‐2 and the close contact kept by domestic dogs with their owners, it became imperative to understand the role of dogs in the epidemiology of the disease and in the virus transmission. In the present study, we determined the presence of virus and described the long‐term immune effects of SARS‐CoV‐2 in 24 dogs exposed to SARS‐CoV‐2 in the domestic environment. Our findings highlight that only a subset of dogs, naturally exposed to SARS‐CoV‐2, exhibit a humoral response to the new virus (close to 17% had IgM antibodies and close to 33% has IgG antibodies). We identified for the first time SARS‐CoV‐2‐specific IFN‐γ‐secreting cells in dogs (approximately in half of our dogs). While 56% of dogs maintained humoral response 8 months, only 22% of dogs maintained cellular response after 4 and 8 months. Although some alterations in blood parameters and proinflammatory cytokines were described, there was no evidence indicating an exacerbated cytokine release process. Considering that none of the animals enrolled in this study showed viral shedding and presented specific immune responses, it is reasonable to propose that the canine immune system in certain companion dogs is effective at blocking the negative effects of viral replication, thereby suggesting that dogs would not be potential transmitters of this pathogen to the other dogs or other species and could aid in promoting collective immunity.