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On the Horizon: OSA Treatments in Development.

Numerous drugs, nanopartides, and antibody-drug conjugates (ADCs) have shown significant promise in targeting and treating OSA. Early results of studies using nanopartides suggest that they may offer potent new therapeutic agents to treat primary tumors as well as to minimize or prevent the recurrence of OSA. There is emerging evidence that bone-targeted therapeutics using bisphosphonates have the potential to significantly improve treatments. ADCs are biopharmaceuticals designed to target and destroy tumor cells while sparing healthy cells. As of 2019, more than 50 pharmaceutical companies are researching the possibilities of ADCs.

* PetCure Oncology, in collaboration with Varian Medical Systems, is currently accepting patients into a clinical trial to evaluate dogs that receive SRS/SRT to treat OSA of the appendicular skeleton. Early data suggests that SRS/SRT can lead to longer median survival time; the study will analyze whether SRS/SRT increases the circulation of immune cells that are responsible for attacking cancer.

* The Blue Buffalo Veterinary Clinical Trials Office at The Ohio State University Veterinary Medical Center is researching a novel anti-cancer drug for dogs with OSA that has metastasized to the lungs. The drug is a chemically synthesized compound (PAC-1) that selectively induces cell death in cancerous cells. The study will evaluate the ability of the drug to decrease the size and growth of lung metastases in dogs when administered in combination with doxorubicin.

* Because the presence of tumor-associated macrophages (TAMs) in bone tumors has been shown to be potentially associated with survival time, the Flint Animal Cancer Center at Colorado State University is conducting a study to develop a noninvasive way to determine how many TAMs are present in bone tumors through the use of an Ultra-Small Paramagnetic Iron Oxide Particle MRI for Imaging.

* Auburn University in Alabama is evaluating zoledronate for treatment of pulmonary nodules associated with OSA metastasis. Bisphosphonates have documented efficacy for control of cancer-associated bone pain and recently have been investigated for its ability to induce cancer cell death as well interfere with metastasis.

* Colorado State University Animal Cancer Center is conducting a study to predict which of the standard chemotherapy protocols will be most effective against an individual dog's tumor and determine if this will provide for longer survival rates.

* A ganglioside-targeted cancer vaccine for OSA is being studied in a Phase 1 trial at the University of Florida College of Veterinary College. A previous study of ganglioside (GD3) showed the vaccine caused a measurable immune response and prolonged survival in dogs with melanoma. (Gangliosides are glycosphingolipids that contribute a substantial presence to the outer leaflet of the cell plasma membrane.)

* The University of Minnesota's College of Veterinary Medicine is researching the genetically modified Vesicular Stomatitis Virus (VSV-IFNG-NIS, called VSV for short) for development of a novel oncolytic immunotherapy for OSA. A pilot study of eight dogs with cancer demonstrated VSV to be safe. Two additional separate studies (12 additional dogs with cancer) found similar results.

* Veterinary Oncology Services in Middletown, NY, is conducting clinical trials to evaluate the benefit of treating OSA (as well as mammary cancer and transitional cell carcinoma) with a genetic DNA telomerase cancer vaccine along with a genetic HER2 cancer vaccine. The goal is to combine these two treatments as a synergistic attack against two different paths of cancer development. Because telomerase is not expressed in most differentiated cells, it is an ideal target for cancer therapeutics.

* Veterinary Oncology Services is also testing whether an adenovirus-based vaccine followed by a DNA plasmid administered via electrogene transfer can elicit anti-tumor immunity and increase survival times for dogs with OSA. The vaccine targets the Her2/neu pathway of tumorigenesis allowing the body's immune system to battle the cancer.

* Aratana Therapeutics has developed an immunotherapy vaccine that uses a lyophilized formulation of a modifiedlive, attenuated, recombinant HER2/neu-expressing strain of Listeria (AT-014) that activates cytotoxic T cells. It received its conditional license from the USDA in December 2017 for the treatment of dogs 1 year or older diagnosed with appendicular OSA.

The vaccine is administered in a series of three doses given three weeks apart, with boosters every six months. The nonlyophilized (liquid) form of this therapeutic was administered to dogs with appendicular osteosarcoma following amputation or limb salvage surgery and chemotherapy consisting of four doses of carboplatin. The median disease-free interval was 615 days and median survival time was 956 days for the 18 dogs in the study (who had no evidence of metastatic disease at enrollment). Adverse events were mild to moderate and primarily consisted of fever, lethargy, and nausea/vomiting.

Aratana is progressing toward full licensure by conducting an extended clinical field study as required by the USDA. About 24 veterinary oncology practices throughout the U.S. are participating in the extended field study and have the vaccine available.

ADXS31-164, the nonlyophilized, frozen form of the USDA conditionally licensed therapeutic AT-014, has not been licensed by the USDA and is available only through clinical trial. This form of the vaccine is being employed in a separate clinical trial at 11 participating sites to evaluate the safety and efficacy in dogs with OSA (target enrollment is 100). This study is funded by Morris Animal Foundation and coordinated by the Comparative Oncology Trials Consortium (part of the National Institutes of Health).
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Publication:Whole Dog Journal
Date:Aug 1, 2019
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