“Click chemistry” can be used to more efficiently deliver drugs to treat tumors in large dogs with bone cancer, researchers report.
It’s a process that had previously only been successful in small mice.
In September, researchers from California and Denmark received the Nobel Prize in chemistry for their development of click chemistry, a process in which molecules snap together like LEGO, making them a potentially more efficient transportation device in delivering pharmaceuticals to cancer tumors.
The goal with click chemistry is to maximize the delivery of therapeutic drugs specifically to the cancer tumor to increase effectiveness while minimizing the circulation of those drugs throughout the bloodstream, which may cause dangerous side effects.
“If you want to attack a tumor using the immune system, an antibody is an extremely specific way to deliver a drug or radioactive payload to the tumor, but the problem with antibodies is they are huge molecules that circulate in the bloodstream for days or even weeks,” says Jeffrey Bryan, a professor in the University of Missouri College of Veterinary Medicine and author of the study in Molecular Pharmaceutics.
“If you put a drug or radioactive molecule onto the antibody, you leave radioactivity circulating in the bloodstream for a long time, which can spread to and negatively impact organs, bone marrow, and the liver while not getting as much dose to the specific tumor as you were hoping for.”
For years, many chemists assumed that while click chemistry has been successful in mice, the strategy would not work in large dogs or people because the size of the body might be too big for the two sides of therapy-delivering molecules to find each other and snap, or “click,” together.
Bryan collaborated with Brian Zeglis, an associate professor at Hunter College who specializes in click chemistry, to conduct the first-ever successful proof-of-concept study at the University of Missouri College of Veterinary Medicine.
Using click chemistry, researchers delivered doses of radiopharmaceuticals to the tumors in five dogs that weighed more than 100 pounds and had bone cancer.
“It is a huge step forward for the field to show that this worked in a human-sized body,” Bryan says. “Going forward, this may pave the way for click chemistry to be used to help humans with cancer in the future.”
Bryan has researched veterinary and comparative oncology for nearly two decades. He says some dogs with one known bone tumor have additional bone tumors hiding in their body’s skeleton. An additional benefit of studies involving imaging scans and click chemistry is the ability to discover if additional cancer tumors are located in a dog’s skeleton and affecting their health.
“Osteosarcoma, a common form of bone cancer, impacts both dogs and people, and it causes severe pain, limping, swelling in the limbs, and treating the bone tumors with various radiation therapy and immune therapy approaches to take away the pain is something I am passionate about,” Bryan says. “Everything we learn about treating these dogs can be translated to help humans down the road.”
The MU College of Veterinary Medicine is the site of clinical trials for cancer that attract people and their pets from California, Florida, New York, and states across the country.
“It is heartwarming to be a part of it because the patients’ families realize it is not just about better outcomes for their specific dog, but they are also contributing to better outcomes for other dogs in the future and hopefully better health outcomes for people as we translate these advances from the dogs to the human side,” Bryan says.
While this was a successful proof-of-concept imaging study involving click chemistry, Bryan’s long-term goal is to develop a therapy using radiopharmaceuticals, potentially involving an antibody-targeting molecule, to treat dogs with bone cancer that may not be well enough for other treatments that involve surgery.
In 2020, Bryan collaborated with ELIAS Animal Health to create a precision medicine approach—a vaccine from a dog’s own tumor—to target and kill cancer cells in dogs suffering from osteosarcoma. The success of the treatment in dogs led the Food and Drug Administration to grant a rare fast-track designation for ELIAS Animal Health’s parent organization, TVAX Biomedical, to study the ELIAS immunotherapy approach to treat glioblastoma multiforme, a cancerous brain tumor in humans.
“The last dog that participated in that study just died a few weeks ago, five years out from their original diagnosis of bone cancer, and the dog never relapsed with its cancer, so the dog was able to live the rest of its life cancer-free due to the immunotherapy,” Bryan says.
“Our overall goal is to come up with different tools in our toolbox to effectively help treat dogs with cancer, and one day even people, too.”
Hunter College funded the work.
Source: University of Missouri
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