Mason, assistant professor of pathobiology and clinical studies in Penn’s School of Veterinary Medicine, and Paterson, professor of microbiology in Penn’s Perelman School of Medicine and associate dean for research and professor of nursing in the School of Nursing, are collaborating on a project to further develop cancer immunotherapies that are already showing promise in both canine and human patients.
The One Health Award, a new Award for Excellence in promoting One Health Initiatives and Inter-professional Education, was established this year by the deans of the four health schools at Penn — Medicine, Nursing, Veterinary Medicine and the School of Dental Medicine. The award recognizes exemplary contributions toward expanding interdisciplinary education and improving health care and will be presented at the international “Feeding Cities” conference at Penn in March.
“We do an enormous amount of collaborative research among all four schools,” said Joan Hendricks, dean of Penn Vet. “We’re doing increasing levels of inter-professional student education, and we’re starting to look into community outreach. We wanted to have a venue for recognizing these accomplishments.”
Yvonne Paterson has worked for many years to develop strategies to harness the immune system to treat cancer. Her laboratory pioneered the use of the bacterium Listeria monocytogenes to induce immune responses against tumors. For the past 10 years her work has focused on developing immunotherapies that specifically target cervical and breast cancer.
Since cervical cancer is particularly prevalent in under-developed countries with poor public-health programs and is a significant cause of cancer death for poor and uninsured women in the United States, there is a need to develop an inexpensive and safe therapeutic vaccine against the disease.
Paterson’s approach to cervical cancer vaccine development relies on L. monocytogenes, which is easily and economically grown. She has genetically engineered the bacterium to express an oncogene found in the human papilloma virus, a pathogen associated with certain types of cervical cancer. A Phase 1 trial using this technique had promising results, and Phase II trials are currently enrolling and treating patients. Early results indicate the technique is effective.
Using a similar approach, Paterson was part of the development of another Listeria-based vaccine known as Lm-HuHER2, which targets the antigen HER2/neu, found on certain types of breast cancers. This vaccine is awaiting clinical trials for breast cancer.
Nicola Mason, a clinical veterinarian specializing in companion animal medicine, earned her Ph.D. in immunology at Penn, during which time she worked with Paterson and her lab. After joining the Penn Vet faculty, Mason focused her research on novel immunotherapeutic approaches to canine cancer. While in the process of identifying novel tumor-associated antigens in canine cancer that can be used as targets for immunotherapy, Mason discovered that some of her canine patients with osteosarcoma, a highly aggressive bone cancer, over-express HER2/neu on their tumors.
Aware of Paterson’s work in developing Lm-HuHER2, Mason discussed with her the possibility of using the Lm-HuHER2 vaccine in dogs. By evaluating the effects of the vaccine in dogs with aggressive bone cancer, they reasoned that they could verify the vaccine’s safety in a relevant, spontaneous, large-animal model. The canine studies could also allow them to determine whether the vaccine provides clinically relevant therapeutic effects, prolonging the dogs’ overall survival, which has typically averaged about one year.
Penn Vet is now actively recruiting canine patients to participate in a pilot study of Lm-HuHER-2 in dogs with bone cancer. Only those dogs with a histological diagnosis of osteosarcoma and who have undergone limb amputation and standard chemotherapy (four doses of carboplatin) for the treatment of osteosarcoma and whose tumors express HER-2 are eligible for the study.
Six dogs already have entered the study and been safely dosed with the Listeria vaccine. As many as 18 dogs are targeted to be treated. Paterson and Mason are pleased with the safety profile of the cancer vaccine in dogs, which closely matches what has been observed in humans.
Because of the ease of administration and the economy of this vaccine, this treatment option could enter into standard clinical treatment for dogs with osteosarcoma. In addition, validation of Listeria as a cancer immunotherapeutic in dogs could lead to extending the use of some of the vaccines designed for use in human cancer to similar canine cancer, underscoring this as a true “one health initiative.”