When James Bianco, M.D., and Jack Singer, M.D., co-founded Cell Therapeutics (CTI; www.cticseattle.com) in 1992, both were oncologists working at an institution that had won a Nobel Prize for pioneering dose-intensive chemotherapy. However, looking 15 years ahead, “we didn’t think that more intensive chemotherapy would be the best solution for patients,” explains Dr. Bianco, president and CEO of Cell Therapeutics in Seattle, WA.
Their mission was to reduce chemotherapy doses by pioneering less toxic and more effective treatments. The company’s motto, Making Cancer More Treatable, is achieved by developing more targeted treatments to prolong life with fewer side effects.
The overall strategy at Cell Therapeutics is to take leading cancer treatment drugs and improve the formulation through the company’s drug delivery platform or acquire companies with promising compounds. Although new cancer drugs like Herceptin or Gleevec specifically target particular tumors, such biotherapeutics account for just 1% of all sales of therapeutic agents worldwide. CTI focuses on four major classes of chemotherapeutic agents that make up more than 90% of chemotherapy sales—taxane, camptothecin, platinates, and anthracycline.
“We see these chemotherapies as the cornerstone of any cancer treatment program for the next 10–20 years,” says Dr. Bianco. “Our portfolio strategy is to develop the next generation of these molecules to address the limitations of the currently marketed products.”
Cell Therapeutics’ drug delivery platform is based on biodegradable polyglutamate polymers linked to existing chemotherapeutics, such as paclitaxel, the active ingredient in Taxol®, one of the most widely prescribed chemotherapies for cancer. The polyglutamate technology was licensed from the University of Texas M.D. Anderson Cancer Center in Houston. CTI holds an exclusive license to the methods.
Cell Therapeutics’ polymer technology can deliver therapies directly to tumors without the need for vectors or direct injections. The amino acid component of the polymer can be altered to target tissues of choice. “Our polymer technology has the potential to exploit the genomic basis of disease and improve future therapeutics,” Dr. Bianco says.
The company’s polyglutamate polymer formulation of paclitaxel, called Xyotax™, does not damage healthy tissue because the polymer inactivates paclitaxel until it reaches tumor cells. Xyotax preferentially favors tumor tissues, which have leaky blood vessels that are more porous to polyglutamate than healthy blood vessels. Once trapped inside tumors, enzymes break down the protein polymer and release paclitaxel.
Since Xyotax localizes in tumors, a higher dose of paclitaxel can be delivered in a shorter time period and with fewer side effects. “Our technology has the ability to create the first biologically enhanced chemotherapeutic agent,” states Dr. Bianco.
So far, the polyglutamate polymer technology has been applied successfully to taxane, generating Xyotax, and camptothecin, producing CTI-2106. In 2003, Cell Therapeutics acquired Novuspharma in Milano, Italy, and its anthracycline derivative pixantrone, which may not cause severe cardiac damage as the current anthracyclines do. “Having a more potent anthracycline that does not cause heart damage could represent a major advance in anthracycline therapies for breast cancer, lymphoma, and leukemia,” Dr. Bianco points out.
Through the acquisition of Novuspharma Cell Therapeutics also obtained a first-in-class bis-platinate compound that disrupts both DNA strands in tumors. The current clinical platinates contain just one platinum molecule that can damage only a single strand of DNA. A stronger platinate that targets both DNA strands “can overcome tumors that develop resistance to platinum,” Dr. Bianco notes.