ILLUSTRATION: JEFFREY PELO
A tiny idea with huge implications in the fight against cancer
City of Hope researchers have opened a clinical trial of a new “nanomedicine” to fight cancer. Although it is too early to report results, researchers are enthusiastic about the innovative technology’s potential.
The clinical trial combines a synthetic polymer (a long molecule) and camptothecin, a very powerful chemotherapy, into a new experimental drug called IT-101.
Researchers designed the polymer to safely deliver the camptothecin directly into tumor cells and provide slow release of the drug once there. Physicians hope the method fights tumors more powerfully than traditional chemotherapy — with fewer accompanying side effects, according to Yun Yen, M.D., Ph.D., director of the Department of Clinical and Molecular Pharmacology and 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 the California Institute of Technology who conceived the idea for the nanodrug after seeing chemotherapy’s effects firsthand.
The engineer — Mark Davis, Ph.D., the Warren and Katharine Schlinger Professor of Chemical Engineering at Caltech — is now part of City of Hope Cancer Center’s Experimental Therapeutics Program, as well as a member of the National Academy of Engineering and the National Academy of Sciences. But in 1996, he visited City of Hope for much different reasons.
Diagnosed with breast cancer, 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 to deliver therapy. Over three months in the mid-1990s, while his wife was in treatment, Davis pored over materials in City of Hope’s 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 his 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 chemotherapy always has been problematic because side effects limit the dosage that physicians can safely give patients.
But “minimizing these side effects gives us greater flexibility in the dosing frequency,” said Yen, also a professor of medical oncology at City of Hope. “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.”
The drug, IT-101, measures about 35 nanometers in length. (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.
KAMINSKY PRODUCTIONSYun Yen
Size is critical, according to Davis. “The polymer–based nanoparticle is small, but it’s huge compared to the tiny molecules that compose a drug. Comparatively speaking, 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.”