A new cancer therapy, combining fragments of human antibodies with specially designed nanoparticles, permanently eradicated colon cancer in treated mice, a multi-institutional team of researchers has found. The result of the “hit and run” drug delivery system, published in the March issue of Advanced Therapeutics, is the culmination of more than five years of collaboration between Cornell, Memorial Sloan Kettering Cancer Center (MSKCC) and the bio pharmaceutical company AstraZeneca.
“I’ve seen great results before, but I’ve never seen anything that eradicates tumors like this,” said study leader Dr. said Michelle Bradbury, director of intraoperative imaging at MSKCC and professor of radiology at Weill Cornell Medicine. .
Other authors include Ulrich Wiesner, Spencer T. Olin Professor in the Department of Materials Science and Engineering, Cornell Engineering; and J. Anand Subramony, vice president of protein engineering research and development at AstraZeneca at the time of the study.
Targeted cancer treatments such as vaccines and nanoparticle therapies have seen limited clinical use because of the limitations of each treatment, but the new treatment — a variation of what researchers call the Cornell factor, or C factor – combines the best features of both. one ultra-small, efficient system.
Because the silica nanoparticles are only 6 nanometers in size, the C’ point is too small to penetrate the tumor and pass through the organ once it is inserted into the body. Wiesner first developed them more than 15 years ago and, in collaboration with Bradbury, published a 2018 study that found that nanoparticle-based hybrids are effective in targeting tumors.
This collaborative project with AstraZeneca sparked the search for a new type of immuno-conjugate therapy through molecular engineering.
AstraZeneca has “site-engineered” a defective antibody to attach effectively to the C-spot and target the HER2 protein associated with colon cancer. The team improved the binding of the fragment above the C site, with a special antibody developed by AstraZeneca. This allowed the nanoparticles to carry about five times more drugs than most vaccines.
The final product is a type of spot C, which has an anti-cancer sheet loaded with a large drug charge, combined with a conjugate treatment of anti-cancer drugs under 7 nanometers – the first type. researchers.
“We describe the mechanism as ‘hit and run’ because C-spots” target the tumor microenvironment and kill tumor cells or eliminate them from the body, Wiesner said. from the failure of the kidneys because of them. small size, thus reducing the unexpected accumulation and effects associated with toxicity.
Mice with gastric cancer received three treatment regimens. Not only did the treatment eradicate the disease in all mice, but there was no evidence of tumor recurrence after nearly 200 days.
“Typically, you have to combine that treatment with other treatments to see the same kind of long-term results,” Bradbury said. “It showed that the team’s hard and hard work – years spent on stoichiometry and advanced chemical development – had paid off.”
Bradbury highlighted the transformation of the C’ point platform and said that he intends to use it not as a substitute for preventive treatment, but as a supportive tool that can be adapted to different types of cancer type and condition.
“C-spots have become effective and efficient in cancer treatment. They have completely eliminated the tumor, even at the cellular level,” said Wiesner. “This is what we expected and it supports our first decision to bet on the therapeutic application of the C-spot.”
Source: Cornell University.
