"Click" chemistry may help treat dogs with bone cancer

In September, researchers from California and Denmark were awarded the Nobel Prize
in Chemistry for their achievements in "click" chemistry.
Click chemistry is a process by which molecules come together like Lego bricks, making them a potentially more efficient transport device for delivering drugs to cancerous tumors
.

Now, in a recent study, a researcher at the University of Missouri has successfully shown for the first time how click chemistry can be used to more effectively deliver drugs to large dogs with bone cancer to treat tumors — a process that has previously been successful only in mice
.

"If you want to attack a tumor with your immune system, antibodies are a very specific way of delivering drugs or radioactive payloads to tumors, but the problem with antibodies is that they are large molecules that circulate in the blood for days or even weeks," said Jeffrey Bryan, an associate professor at the University of Michigan School of Veterinary Medicine and author
of the study 。 "If you put a drug or radioactive molecule on an antibody, you let the radioactive material circulate in the bloodstream for a long time, it spreads to the organs, bone marrow and liver, and negatively affects the organs, bone marrow and liver, and the dose for a particular tumor is not as large
as you would like.
"

The goal of Click Chemistry is to maximize the delivery of therapeutic drugs to cancer tumors to improve efficacy while minimizing the circulation of these drugs in the bloodstream and causing dangerous side effects
.

From rat to man's best friend

For years, many chemists believed that while click chemistry had been successful in mice, this strategy did not work in large dogs or humans, whose bodies could be so large that the molecules that deliver the therapeutic effects could not find each other and "click"
together 。 Brian teamed up with Brian Zeglis, an associate professor specializing in click chemistry at Hunter College in New York, to conduct the first successful "proof-of-concept" study
at the MU College of Veterinary Medicine.
By clicking on chemistry, doses of radiopharmaceuticals were administered specifically to the tumors of 5 bone cancer dogs weighing more than 100 pounds
.

Bryan said: "This is a big step forward in the field and shows that this also works
on human-sized bodies.
Going forward, this could pave the way
for click chemistry to be used in the future to help humans with cancer.
”

Bryan has been engaged in veterinary oncology and comparative oncology research for nearly 20 years
.
Some dogs that are known to have a bone tumor hide other bone tumors
in their bones, he said.
Another benefit of studies involving imaging scans and click chemistry is the ability to detect whether there are additional cancerous tumors in dogs' bones and affect their health
.

"Osteosarcoma is a common bone cancer that affects both dogs and people, it causes severe pain, limping, swelling of the limbs, and treating bone tumors with various radiation therapies and immunotherapies to eliminate pain is something I am passionate about
at the University of Michigan," Bryan said.
Everything we learn about treating these dogs can be translated into help
to humans.
”

A leader in treating human and pet cancers

Last year, MU College of Veterinary Medicine received more than $14 million in federal research funding from the National Institutes of Health, the site for cancer clinical trials that attract people and their pets
from California, Florida, New York and across the country.

While this is a successful "proof-of-concept" imaging study involving click chemistry, Bryan's long-term goal is to develop a treatment using radiopharmaceuticals, possibly involving antibodies targeting molecules, to treat dogs with bone cancer that may not be able to undergo other treatments
through surgery.

"This study is also an example of precision medicine and is a key part of the University of Michigan's Next Generation Precision Health Program because we are using molecules associated with specific tumors to deliver therapeutic doses
," Bryan said.
We work with the University of Michigan Research Reactor, Molecular Imaging and Therapeutics Center and Washington University in St.
Louis, so it's a team effort
.
”

In 2020, Bryan partnered with ELIAS Animal Health to create a precision medicine approach — a vaccine extracted from a dog's own tumor to target and kill cancer cells
in dogs with osteosarcoma 。 The success of the treatment in dogs led the Food and Drug Administration to grant a rare fast-track license to TVAX Biomedical, the parent company of ELIAS Animal Health, to study ELIAS immunotherapy for glioblastoma multiforme, a malignant brain tumor in humans
.

"The last dog involved in this study died just a few weeks ago, five years after they were originally diagnosed with bone cancer, and the dog's cancer never returned, so the dog was able to live the rest of its cancer-free life
thanks to immunotherapy," Bryan said.
Our overall goal is to find different tools in our toolbox that will effectively help treat dogs with cancer and one day even humans
.
”

Charles A.
Maitz, Samantha Delaney, Brendon E.
Cook, Afaf R.
Genady, Rebecca Hoerres, Marina Kuchuk, Georgios Makris, John F.
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Hennkens, Jeffrey N.
Bryan, Brian M.
Zeglis.
Pretargeted PET of Osteodestructive Lesions in Dogs.
Molecular Pharmaceutics, 2022; 19 (9): 3153