Californian and Danish researchers have been awarded the Novel Prize in Chemistry for developing “click” chemistry, a method of linking molecules like LEGOs that could be a more efficient way to deliver drugs to cancerous tumors. In a new study, a University of Missouri scientist has successfully demonstrated for the first time how click chemistry can be used to more effectively deliver drugs to treat tumors in large dogs with bone cancer. . Previously, this method had only been successful in small mice.
“If you want to attack a tumor using the immune system, an antibody is an extremely specific way of delivering a drug or a radioactive load to the tumor, but the problem with antibodies is that it’s huge molecules that circulate in the blood for days or even weeks,” said Jeffrey Bryan, associate professor at the MU College of Veterinary Medicine and author of the study. “If you put a drug or a radioactive molecule on the antibody, you let radioactivity circulate in the bloodstream for a long time, which can spread and negatively impact organs, bone marrow, and liver while not getting as much dose to the specific tumor as you were hoping for .”
The goal of click chemistry is to maximize the delivery of therapeutic drugs specifically to the cancerous tumor to increase efficacy while minimizing the release of these drugs into the bloodstream and causing dangerous side effects. From mouse to man’s best friend
Many chemists believed for many years that although click chemistry was successful in mice, the strategy would not be effective in large dogs or people due to the possibility that body size would prevent both sides of the molecules delivering therapy find each other and ‘click’ together. The first-ever successful “proof-of-concept” study at the MU College of Veterinary Medicine was conducted by Bryan in partnership with Brian Zeglis, an associate professor at Hunter College in New York who specializes in click chemistry. Five dogs with bone cancer weighing more than 100 pounds each received doses of radiopharmaceuticals delivered exactly to the tumors via click chemistry.
“It’s a huge step forward for the field to show it worked in a human-sized body,” Bryan said. “In the future, this could pave the way for click chemistry to help humans with cancer in the future.” Bryan has been researching veterinary and comparative oncology for nearly two decades. He said some dogs with a known bone tumor had additional bone tumors hidden within the skeleton of their bodies. An added benefit of studies involving imaging scans and click chemistry is the ability to discover if other cancerous tumors are located within a dog’s skeleton and are impacting their health.
“Osteosarcoma, a common form of bone cancer, affects both dogs and humans, and it causes severe pain, lameness, swelling of the limbs, and treatment of bone tumors with various approaches of radiation therapy and d “Immunotherapy to eliminate pain is something I’m passionate about here at MU,” Bryan said. “Everything we learn about treating these dogs can be translated to help humans down the road.” in the treatment of cancer – for people and pets
Cancer clinical trials are conducted at the MU College of Veterinary Medicine, which received more than $14 million in federal research funding from the National Institutes of Health last year. Participants and their pets come from California, Florida, New York and other states to participate. “It’s heartwarming to be a part of this, as families of patients realize it’s not just about better outcomes for their specific dog, but also contributing to better outcomes for other dogs at the same time. future and hopefully to better health outcomes for people as we translate these advances from dogs to the human side,” Bryan said.
Although this is a successful “proof of concept” imaging study involving click chemistry, Bryan’s long-term goal is to develop a therapy using radiopharmaceuticals, potentially involving a molecule targeting the antibodies, to treat dogs with bone cancer that may not be good enough for other treatments that involve surgery. “This research is also an example of precision medicine, a key component of MU’s NextGen Precision Health initiative, as we use the molecules associated with the specific tumor to deliver the therapeutic dose of treatment,” Bryan said. “We collaborate with the MU Research Reactor, the Molecular Imaging and Theranostics Center, and Washington University in St. Louis, so it’s a team effort.”
Bryan worked with ELIAS Animal Health in 2020 to develop a precision medicine strategy – a vaccination derived from a dog’s own tumor – to target and eradicate cancer cells in dogs with osteosarcoma. The Food and Drug Administration has granted ELIAS Animal Health’s parent company, TVAX Biomedical, a unique fast-track designation to study the ELIAS immunotherapy strategy to treat glioblastoma multiforme, a malignant brain tumor in humans, due to efficacy of treatment in dogs.
“The last dog that participated in this study just died a few weeks ago, five years after his initial diagnosis of bone cancer, and the dog never relapsed with his cancer, so the dog was able to live the rest life with cancer-free through immunotherapy,” Bryan said. “Our overall goal is to have different tools in our toolbox to effectively help treat dogs with cancer, and even one day people. too.” (ANI)
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