The leader in Veterinary Biologic solutions is pleased to announce the launch of K-9 ACV, a new autologous innovation for the treatment of canine cancer available to the general practice.
Highly experienced cancer researchers at the University of Kentucky (Drs. John Yannelli and Don Cohen) have selected MediVet Biologics as a partner due to their success in the market through launching novel autologous products for Veterinarians such as Adipose Derived Stem Cell treatments & Platelet Rich Plasma. Their products and services continue to impact the Veterinary market medically. Dr. Yannelli has been involved in immunotherapy research since 1985 and has contributed significantly to the development of treatments for melanoma. Dr. Cohen’s research lab is focused on understanding immunological mechanisms which regulate the onset and persistence of inflammation in acute and chronic disease settings.
Cancer in Dogs
Greater than fifty percent of dogs over the age of ten will eventually develop cancer, making cancer the leading cause of death in dogs. Canine cancers include both solid tumors (sarcomas, carcinomas, and lymphomas) and liquid tumors (leukemias). Each tumor type has the capacity to metastasize to distant anatomic sites if left untreated, further impacting life expectancy of dogs with cancer. While cancer screening programs for early detection in humans have led to significant reductions in cancer deaths, cancer screening for early detection in dogs lags far behind what is available for humans. Consequently, canine cancers are usually diagnosed in later stages of disease, making them more difficult to treat effectively and increasing the likelihood of tumor recurrence. Appropriately designed tumor vaccines can break immune tolerance, leading to an effective anti-tumor immune response which can improve survival and quality of life in veterinary patients. Melanoma in humans has been shown to be quite immunogenic and accordingly immunotherapeutic approaches for cancer have shown promise for melanoma, as well as for other immunogenic tumors. The early work of scientists at the NCI and other centers around the world has led to FDA approval of the first and only therapeutic human cancer vaccine in 2010.
Individual molecule-targeted vaccines require precise knowledge of the targeted molecules before vaccine development can be pursued. Given that many (if not all) tumors can be recognized by the immune system, a broader and possibly better approach for vaccine development may be to use the entire tumor cell (autologous tumor) as the basis for the vaccine and to deliver it to patients in a manner that breaks tolerance to tumor cell antigens and promotes strong anti-tumor immunity.
Ideal Canine Patients for K9-ACV
- Dogs of any weight or breed, greater than 1 year of age
- Dogs with any peripheral solid tumor that is accessible for surgical resection. Tumor examples include:
- Mammary Tumors
- Melanoma (Oral) Soft Tissue Sarcoma
- Digital tumors (squamous cell carcinomas and melanomas)
- Skin tumors (melanoma, squamous cell carcinoma, basal cell carcinoma, sebaceous gland tumors, round cell tumors, mast cell tumors, etc.)
- Removable tumor mass must be at least 5 grams
- It is suggested that the dog has a predicted survival of greater than 3 months
Canine Patients to Exclude
- Chemotherapy treatment within the last week
- Radiation therapy within the last week
- Any previous form of immunotherapy
- Prior hormonal or biological therapy directed at the tumor
- Skin ulceration covering site of resected tumor
- Presence of an active systemic infection
- Any vaccination within the last 4 weeks
- Dogs treated with corticosteroids or other immunosuppressant within 3 weeks
- Pregnant during vaccine schedule
Please visit the link below to utilize our online booking for Medivet Biologics K9-ACV cancer service.
K9-ACV stands for Canine Autologous Cancer Vaccine. Cancer cells can be recognized as foreign by the immune system if those cancer cells are presented to the immune system in a manner that “breaks immune tolerance.” Decades of research in mouse and human models have shown that tumor cells are very much like normal cells in that they express self-antigens that the body is taught to ignore early in development and throughout life. An immunosuppressive environment produced by growing tumors promotes an immune response toward the tumor that is ineffective, allowing the tumor to grow unchecked.
An appropriately designed tumor vaccine can break this cycle of tumor immunosuppression, generating tumor-specific immune cells that have effective anti-tumor reactivity, improving survival and quality of life in veterinary patients. The K9-ACV vaccine is specifically designed to make the patient’s tumor appear foreign, thus inducing an effective anti-tumor immune response, similar to an immune response against viral or bacterial infections.
How is K9-ACV different from previous experimental cancer vaccines?
Previous experimental cancer vaccines were designed to induce the generation of tumor- specific antibodies. Many newer cancer immunology studies have shown that while antibodies contribute to effective tumor immunity, development of tumor-specific Tlymphocytes is critical for cancer immunotherapy. Newer antibody therapies appear beneficial because they enhance the function of T lymphocytes. Thus, future effective therapies will likely incorporate a dual approach. K9-ACV is designed to induce both tumor-specific T lymphocytes and tumor-specific antibodies with an autologous vaccine approach. This we believe will lead to a stronger and more effective immune response to a patient’s tumor.
What about histopathology of the sample?
MediVet Biologics has selected the smallest volume possible to process the vaccine. This quantity allows for histopathologic assessment, preparation of multiple vaccine doses and safety testing, as well as immunologic assessment which aids in the interpretation of the clinical results and design of future improved approaches. Research by the investigators has shown that on a per gram basis, adequate numbers of viable tumor cells and host leukocytes are available for the vaccine preparation with this small volume of tumor tissue.
What if the cancer comes back non-cancerous from my histopathology lab?
Should the report come back non-cancerous from your diagnostic lab, please contact the help line immediately to suspend the service. Once notified the service will be suspended and no additional charges will be incurred.
What is the injection protocol?
The injection protocol involves three administrations of a killed tumor vaccine. Each dose is administered on a monthly basis as shown in the schedule provided. We ask that the entire 1 ml volume of each vaccine dose be administered intradermally, although some leakage into subcutaneous tissue is expected. The vaccine will appear cloudy, which is not a problem. The vaccine consists of cellular fragments obtained from 10 million cells from the tumor, which accounts for the cloudy nature of the vaccine. All vaccines are rigidly tested for sterility and are not released to your practice unless sterility criteria are met.
What side effects should the owner be made aware of?
In similar human tumor vaccine studies, hundreds of vaccines have been administered on an out-patient basis. Following vaccination, patients are normally observed for roughly 1 hr. for any adverse event which in the experience of the investigators has been minor. Minor fever and minimal inflammation may occur over the next 48 hours. This inflammatory response is beneficial for the success of the vaccine.
Once the treatment protocol is underway, what will my role be in the diagnostics to assist the patient?
Once the vaccine is administered, your role will be to monitor the dog’s health, behavior and quality of life. Blood draws are required at four specified time points as shown in the schedule provided. These blood draws are critical for the proper evaluation of vaccine efficacy, so it is important to adhere to the schedule for blood draws.
Can I continue drug treatments in patients enrolled in the K9-ACV trial?
Anti-inflammatory drugs, such as NSAIDs and acetaminophen, can reduce effectiveness of vaccines. Consequently, anti-inflammatory therapies should be discontinued at least one week before the initial vaccination. Patients should remain off these drugs for the entire protocol, including two weeks following the final vaccine dose. However, the final decision must be made by the individual Veterinary care-giver who knows explicitly the needs of the particular patient.
John Yannelli, PhD
Dr. John Yannelli (Associate Professor) received his PhD in anatomy from Virginia Commonwealth University and performed a postdoctoral fellowship in cellular and molecular immunology at the University of Virginia Medical School. He rose to division chief of cellular therapeutics in Biotherapeutics, Inc. before becoming Head of the Cellular Immunotherapy Laboratory at the NIH National Cancer Institute. At the NCI, he was a member of a pioneering research team to develop cell-based cancer immunotherapies including the first gene therapies performed in human cancer. Dr. Yannelli has been a faculty member in the UK College of Medicine and a member of the UK Markey Cancer Center for over 20 years where he has performed a number of successful NIH-funded clinical trials in humans with lung cancer. Dr. Yannelli has published nearly 100 articles and book chapters on the immunotherapy of human cancer and continues research to improve immunotherapeutic approaches to treat cancer.
Yannelli, J.R., Tucker, JA, Hidalgo, G., Perkins, S., Kryscio, R., and Hirschowitz, E. (2009) Characteristics of PBMC obtained from leukapheresis products and tumor biopsies of patients with non small cell lung cancer (NSCLC). Oncology Reports, 22:1459-1471.
Hirschowitz, E.A. and Yannelli, J.R., (2009) Immunotherapy of Lung Cancer. Proceedings of the American Thoracic Society, 6:224-232.
Hirschowitz, EA., Hidalgo, G., and Yannelli, JR., (2007) Follow-up analysis of non small cell lung cancer patients immunized with immature antigen pulsed dendritic cells. Lung Cancer, 57:365-372.
Best, A., Hidalgo, G., Mitchell, K., and Yannelli, J.R., (2007) Issues concerning the large scale cryopreservation of PBMC for immunotherapy trials. Cryobiology, 54:294-297.
Yannelli, JR., and Wroblewski, J., (2007) Identification by cDNA cloning of minor antigens and HLA-C3 as targets in mixed lymphocyte tumor cell (MLTC) cultures between peripheral blood of non small cell lung cancer (NSCLC) patients and an allogeneic NSCLC line. Cancer Biotherapy and Radiopharmaceuticals., 22: 206-222.
Hirschowitz, EA., Hiestand, DM., and Yannelli, JR., (2006) Active immunotherapy for lung cancer. Journal of Thoracic Oncology, 1:93-104.
Yannelli, JR, Sturgill, J., Foody, T, and Hirschowitz, E., (2005) The large scale generation of dendritic cells for the immunization of patients with non small cell lung cancer. Lung Cancer, 47:337-350.
Yannelli, JR, Sturgill, J., Foody, T, and Hirschowitz, E., The large scale generation of dendritic cells for the immunization of patients with non small cell lung cancer. Lung Cancer, 2005. PDF
Hirschowitz, E.A., Foody. T., Kryscio, R., Dickson, L., Sturgill, J., and Yannelli, J.R., (2004) Clinical investigation of protein based dendritic cell vaccines in NSCLC. J. Clin. Oncol, 22:2208-2815, 2004. PDF
Yannelli, J.R., and Wroblewski, J.M. The cellular immunotherapy of cancer revisited: How far have we progressed? Vaccine, 23:97-113, 2004.
Yannelli, J.R. , Hirscowitz, E., and Wroblewski, J.M. (2003) Growth and functional reactivity of lymphocytes obtained from three anatomic compartments in patients with non-small cell lung cancer. Cancer Biotherapy and Radiopharmaceuticals. 18:735-749. PDF
Bixby, D.L., and Yannelli, J.R., (1998) CD80 expression in an HLA-A2 positive human non small cell lung cancer cell line enhances proliferation and cytotoxicity of -A2 positive T cells derived from normal donors and patients with non small cell lung cancer. International Journal of Cancer., 78:685-694. Wiley InterScience :: Journal :: Article [Abstract]Yannelli JR, Hyatt C, McConnell S, Jacknin L, Hines K, Parker L, Sanders M, Rosenberg SA (1996). The growth of tumor infiltrating lymphocytes from human solid cancers: Summary of a 4 year experience. International Journal of Cancer, 65, 413.
Yannelli JR, McConnell S, Parker L, Nishimura M, Robbins P, Yang J, Kawakami Y (1996). Tumor reactive lymphocytes from 4 distinct anatomic sites. Journal of Immunotherapy, 18, 263.
Rosenberg SA, Yannelli JR, Yang JC, Topalian SL, Schwartzentruber DJ, Weber JS, Parkinson DR, Seipp CA, Einhorn JH, White DE (1994). Treatment of patients with metastatic melanoma using autologous tumor infiltrating lymphocytes and interleukin-2. Journal of the National Cancer Institute, 86:1159.
West WH, Tauer KW, Yannelli JR, Marshall GD, Thurman GB, Orr D, Oldham RK (1987). Constant infusion of recombinant interleukin-2 in adoptive immunotherapy of advanced cancer. New England Journal of Medicine, 316:898
Yannelli JR, Sullivan J, Mandell GL, Engelhard VH (1986). Reorientation and fusion of cytotoxic T lymphocyte granules after interaction with target cells as determined by high resolution cinemicrography. Journal of Immunology, 136:177. PDF