by Mark Wheeler
City of Hope researchers have opened a clinical trial of a new “nanomedicine” to fight cancer, and though it is too early to report patient results, researchers are enthusiastic about the innovative technology’s potential.
Nanomedicine aims to use tiny, engineered molecules as high-tech delivery trucks within the body. Their destination: tumor cells. Their payload: potent chemotherapy drugs.
City of Hope’s nanomedicine clinical trial combines a synthetic polymer and camptothecin, a very powerful chemotherapy, into a new experimental therapeutic called IT-101.
Researchers designed the polymer to safely deliver the cancer-fighting drug directly into tumor cells and provide slow release of the drug once there. Physicians hope the method improves anti-tumor effects — with fewer accompanying side effects.
Yun Yen, M.D., Ph.D., director of the Department of Clinical and Molecular Pharmacology, is the trial’s lead investigator.
The phase I clinical trial is a collaboration with Insert Therapeutics Inc., a company founded by a chemical engineer from Caltech who conceived the idea for the nanodrug after his wife had been successfully treated for breast cancer at City of Hope.
Mark Davis, Ph.D., is the Warren and Katharine Schlinger Professor of Chemical Engineering at Caltech and now part of City of Hope’s Developmental Cancer Therapeutics program, as well as a member of the National Academy of Engineering and the National Academy of Sciences.
In 1996, Davis’ wife, Mary, was under the care of City of Hope’s Stephen J. Forman, M.D., the Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation and a physician in the Division of Medical Oncology & Therapeutics Research. While undergoing treatment, she suffered the side effects common to patients on chemotherapy, including hair loss, loss of appetite and nausea.
Davis vowed to find a better way. Over three months in the mid-1990s, while his wife was at City of Hope, Davis pored over materials in Graff Library to learn about cancer therapies and began to develop his strategy. He used his expertise in creating new materials molecule by molecule, ultimately building the first nanomedicine for cancer from scratch.
But he could not bring his idea to the clinic without knowledgeable collaborators. Davis founded Insert Therapeutics to develop the invention into a product that could be used in humans. Investigators at Insert Therapeutics showed the potential of this new nanomedicine in animals, and Yen worked with company investigators to design the clinical trial that was eventually approved by the Food and Drug Administration. These partnerships brought an inspiration from the patient’s bedside into the lab and back to the bedside.
Now, the resulting nanomedicine developed by Insert Therapeutics is in a human clinical trial only at City of Hope.
As Yen explains, delivering chemotherapeutic drugs always has been problematic because side effects limit the dosage that can be safely given.
But “minimizing these side effects gives us greater flexibility in the dosing frequency,” said Yen, professor of medical oncology. “It also allows us to use combinations of drugs that were previously limited by accumulated toxicity. The result could be used to provide more effective therapies.”
IT-101 measures about 35 nanometers (one nanometer equals one-billionth of a meter, and a single strand of human hair is about 80,000 nanometers across). That is tiny enough to pass through even the smallest blood vessels to get to where cancer has metastasized, and then enter the cancer cells.
Size is critical, according to Davis. “The polymer-based nanoparticle is small, but it’s huge compared to the tiny molecules that comprise a drug; it’s the difference between the size of a soccer ball — the drug molecule — and about half the size of the Goodyear blimp, the polymer device,” he said. “Make the nanomedicine too small and it will be quickly excreted from the body; conversely, if it is too large it won’t allow for good penetration into the tumors.”
The resulting particle is designed to access cancer cells, target growth processes and shut them down by effectively delivering a large payload of drug.
Both Davis and Yen agree such nano-sized medicines have the potential to ultimately become the medical standard in cancer therapy. “This is a perfect example of linking clinical expertise with research expertise to push drug development and cancer treatment to more efficient levels,” said Yen. “Ultimately, this collaboration can only benefit patients through more targeted drug dosages, and hopefully, the virtual elimination of side effects.”
