A new cancer drug that combines antibody fragments with molecularly engineered nanoparticles has permanently eradicated stomach cancer in treated mice, a multicenter team of researchers has found.
‘Hit and Run’ Drug Delivery System Work Featured in March Issue of Advanced Therapeutics culminates more than five years of collaboration between Cornell University, Memorial Sloan Kettering Cancer Center (MSKCC) and biopharmaceutical company AstraZeneca is.
“I’ve seen great results before, but I’ve never seen anything that eradicates tumors like this,” said co-lead author of the study and director of intraoperative imaging at MSKCC. said Michelle Bradbury, Ph.D., professor of radiology at Weill Cornell Medicine.
The other co-first author is Ulrich Wiesner, Professor Spencer T. Olin, Department of Materials Science and Engineering, Cornell Engineering. J. Anand Subramony, Vice President of Protein Engineering Research and Development at AstraZeneca at the time of the study.
Targeted cancer therapies such as antibody therapy and nanoparticle therapy have limited clinical use due to the limitations of each therapy, but researchers have dubbed Cornell Prime Dot (C’ Dot). An evolution of things, the new treatment combines the best attributes of both into an ultra-compact form factor. , a powerfully effective system.
Silica nanoparticles are only 6 nanometers in size, so the C’dots are small enough to penetrate tumors and pass safely through organs when injected into the body. Wiesner first developed them more than 15 years ago, and collaborated with Bradbury on his 2018 study that found hybrids of antibody fragments and nanoparticles to be particularly effective at finding tumors. Announced.
This collaboration with AstraZeneca began the search for new molecularly engineered therapeutic versions of this immunoconjugate.
AstraZeneca has “site engineered” a fragment of the antibody to effectively bind to the C’dot and target the HER2 protein associated with gastric cancer. The team optimized fragment binding to the C’dot surface with a specialized inhibitor developed by AstraZeneca. This allowed the nanoparticles to carry about five times more drug than most antibodies.
The final product was a version of C’dot armed with cancer-targeting antibody fragments and a large drug payload, all packed into a sub-7-nanometer drug-immunoconjugate therapy. According to researchers.
“We describe the mechanism of action as ‘hit and run,'” Wiesner said. Their small size minimizes off-target accumulation and associated side effects and toxicity. “
Mice with gastric cancer received three doses of the therapeutic drug. Not only did this treatment eradicate the disease in all mice, but there was no evidence of tumor recurrence after nearly 200 days.
“This treatment usually needs to be combined with other treatments to get such long-term results,” said Bradbury. “It shows that the very detailed and careful work of this team, who spent years developing stoichiometry and surface chemistry, has paid off.”
Bradbury emphasized the versatility of the C’dot platform, not to be used as an alternative to antibody therapy, but as a complementary tool that can be adapted to different cancer types and other specific patient needs. I said I was assuming.
“C’dots have become very effective and safe in treating cancer. They completely obliterated tumors, even at the cellular level,” Wiesner said. “This is what we finally wanted and further confirms our previous decision to bet on C’dot’s therapeutic application.”
Wiesner and Bradbury said the research behind the new C’dot treatment will continue with Elucida Oncology, a startup they set up to help bring the technology to market. Although Elucida has not used antibody fragments in his current clinical trials of C’dot, this work could be useful in constructing new conjugates that could make use of such fragments in future trials. Helpful they said.
Original: Antibody fragment nanoparticle therapy eradicates cancer
Than: Cornell University School of Engineering | Memorial Sloan Kettering Cancer Center
