02071: Development of a Therapeutic Brain Tumor Vaccine
Grant Status: Closed
Meningiomas are the most common primary brain tumor in dogs that affects more than 10,000 dogs in the U.S. annually. These tumors occur most frequently in older dogs and in certain breeds -- Golden Retrievers, Labrador Retrievers, Boxers, German Shepherd Dogs and Collies -- causing uncontrolled generalized grand mal seizures in most cases. Although the biological behavior of these tumors is generally considered benign, most meningiomas recur less than one year after either surgery or radiation therapy. Furthermore, radiation therapy is expensive, involves many, repeated episodes of general anesthesia, and cause severe adverse effects. Longer survival times can be achieved through special techniques, but most dogs treated undergo more standard surgical removal and/or radiation therapy. Clearly, there is an urgent need for novel therapies to prevent tumor recurrence and increase survival time after surgery. Dr. Pluhar has developed immunotherapy protocols for dogs with gliomas, and recently assessed this strategy in a pilot study treating meningiomas with tumor lysate vaccines. Her data for six dogs showed this approach was safe, feasible and effective. Dr. Pluhar now proposes a larger clinical trial treating 30 dogs with meningioma by surgery alone or surgery followed by vaccines. They expect to see a specific immune response to the vaccines that prevents tumor recurrence. The data from the proposed study will provide further proof of safety and efficacy of vaccine-based therapy to support: 1) more widespread use in dogs and 2) initiation of a Phase I trial for high grade and recurrent meningioma in humans.
Olin, M. R., Pluhar, G. E., Andersen, B. M., Shaver, R., Waldron, N. N., & Moertel, C. L. (2014). Victory and Defeat in the Induction of a Therapeutic Response through Vaccine Therapy for Human and Canine Brain Tumors: A Review of the State of the Art. Critical Reviews in Immunology, 34(5), 399–432. https://doi.org/10.1615/CritRevImmunol.2014011577
Pluhar, G. E., Pennell, C. A., & Olin, M. R. (2015). CD8+ T Cell-Independent Immune-Mediated Mechanisms of Anti-Tumor Activity. Critical Reviews in Immunology, 35(2), 153–172. https://doi.org/10.1615/CritRevImmunol.2015013607
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