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George Aslanidi, PhD, Professor at The Hormel Institute, University of Minnesota, is the recipient of a five-year, nearly $2,500,000 grant from the National Cancer Institute (NCI) at the National Institutes of Health (NIH). The grant was awarded to support the Aslanidi lab’s contributions to a preclinical study aimed at developing a novel AAV cancer vaccine strategy for oral melanoma, which could benefit the health of humans and canines alike.

The study, which is in collaboration with the Veterinary Clinical Investigation Center at University of Minnesota, will investigate the efficacy of an AAV-based vaccine to supplement existing treatments for dogs with oral melanoma in order to limit metastatic spread and cancer recurrence.

Dogs involved in this preclinical study are companion animals who were already diagnosed with oral melanoma and enrolled by their owners, and data gathered will help to determine whether advancing to a human clinical trial is warranted. Dr. Antonella Borgatti of the U of M’s College of Veterinary Medicine is the study’s co-principal investigator.

Because cancers that develop in dogs exhibit similar interactions of factors including genetics, age, and environmental factors that play out in human cancer development, the NCI commonly uses information from studies of canine cancer to help guide studies of human cancer. Previous AAV-based therapies have also been found to be safe for dogs in preclinical trials prior to treatment in humans.

In humans, oral melanoma, also referred to more generally as mucosal melanoma since it can occur in any mucosal membrane, is a rare but aggressive form of cancer. Oral melanoma is more common in dogs, especially older ones that are often facing additional health problems as they age.

For humans and dogs alike, there currently aren’t many ideal treatment options for oral melanoma, especially if the cancer has already spread to other parts of the body. Surgery is often a first resort and may be followed by radiotherapy or chemotherapy, and in humans, immunotherapy, but generally these options have not proven to be very effective, especially after the cancer has metastasized. The lungs are one of the most common sites for initial metastasis in oral melanoma, at which point the cancer will often become incurable due to the number of cancerous sites that need to be removed and the difficulty of operating on lungs.

Oral melanoma is often difficult for pet owners to detect in their dogs since it can often start in remote areas of the mouth that are difficult to notice — so when cancer is identified, it has often already metastasized. Once dogs have been diagnosed with oral melanoma, life expectancy can range from just three to six months.

This AAV-based vaccine, which has been developed over the last decade in Aslanidi’s lab, is designed to target dendritic cells that will eventually train T cells to identify and kill cancerous cells over the short and long term without harmful side effects to other cells and tissues.

Over the course of the study, the dogs with oral melanoma will undergo common existing treatments (surgery, radiotherapy, etc.), while also receiving a single dose of the vaccine.

Then, the animals will have periodic clinic visits for general health evaluations, chest X-rays to determine whether the cancer has metastasized, and they will also have blood collected to determine the strength of their immune responses. The animals’ progress will be monitored alongside treatments for up to nine months, with possible follow-ups after procedures have ended.

“We hope to expand the repertoire of diseases treated by AAV vectors, provide additional therapeutic options for our furry friends, and ultimately for [human] patients,” Aslanidi said.

“If the vaccine is proven to be effective, it will open new opportunities and a way to treat cancer patients,” Aslanidi said. “It might help to limit some of the anxiety and fears the patient may have in the long term. Secondly, it could dramatically reduce side effects often caused by common treatments such as chemotherapy, because it is based on the natural activation of the immune system.”

Aslanidi also extended gratitude to the many lab members past and current who have made it possible for the study to reach its current point, and for the Paint the Town Pink seed grants that helped support much initial research.