In the constant search to find a cure to cancer researchers at the University of Pennsylvania have caught the attention of Novartis, the world’s second-largest drug company. Following promising initial results in their study of genetically modified T-cells, Novartis gave the university $20 million to build a new a cell therapy center in exchange for the rights to sell whatever potential medicine the researchers produce. Merely a year after this deal in August of 2013 Lawrence Corey, an infectious-disease doctor, with funding from Robert Nelsen of Arch Venture Partners and help from Richard Klausner chief medical officer of the DNA-sequencing company Illumina, founded Juno Therapeutics. Juno entered the T-cell field by purchasing patents and licensing rights to T-cell trials in Seattle and at Memorial Sloan Kettering in New York. Since August of 2013 Juno has taken off; in December of 2014 a mere 16 months after its founding they went public raising $304 million in the process. They sold 11 million shares at $24 each in their IPO. By the time the market closed the following day the stock was selling at $35, a 46 percent increase, and had a market valuation of approximately $2.7 billion. In the time since going public the market value has continued to increase reaching $6 billion.
All the excitement about their new approach to treating cancer stems from eliminating the use of chemotherapy in patients with leukemia and lymphoma. T-cell therapy works by removing a patient’s T-cells and introducing them to a virus which genetically modifies them. T-cells have receptor sites which are meant to bond with foreign or harmful antigens and then kill them. The problem with cancer is that tumors are formed from one’s own cells and are therefore not recognized as dangerous. The genetic modification changes the antigens that the T-cell receptor sites are designed for. While most antigens found in tumor cells can be found throughout the rest of the body in healthy and vital organs, Michel Sadelain, a researcher at Memorial Sloan Kettering Cancer Center and one of the scientific founders of Juno, has identified an antigen that is exclusively found in tumor cells and B cells, which are non-essential to human life. This allows scientists to genetically modify T-cells to bond with this specific antigen (CD19) without harming the patient. Upon bonding with the CD19 antigen the T-cells proceed to kill the cell it has bonded with and hence remove the tumor. Sadelain’s discovery was groundbreaking as previously modified T-cells had actually killed patients by bonding with antigens that were not only in the tumor cells but also in vital organs. But methods for preventing genetically modified T-cells from killing other patients do not stop there as “suicide switches” have recently been added to this T-cells. These switches are incorporated in the DNA given to the T-cells and cause the genetically modified T-cells to become inactive when in contact with one does the drug Erbitux.
The research being done by Juno Therapeutics and Novartis is so promising that last summer the U.S. Food and Drug Administration gave them both breakthrough designation so that their leukemia treatment can be approved after only 1 clinical trial. In the meantime the companies have to figure out how they can commercialize the treatment. Currently the centers that are used can not mass produce genetically modified T-cells. In fact the center used by Michael Jensen of Seattle Children’s Hospital, one of the leading hospitals in T-cell cancer research, can only modify the DNA of 10 patients per month and it costs $75,000 to modify the T-cells of each patient. Given the cost and time necessary to modify the T-cells of each patient it seems like the easiest way to commercialize the treatment is it use T-cells not produced by the patient. While T-cells generated in a dish have been successfully used on mice, and other labs are working on instruments to pump the new DNA into T-cells through electricity or pressure, currently all trials involve removing the T-cells from a patient’s body, genetically modifying them, and then reinserting them via a ten minute IV drip. If labs can engineer T-cells successfully fight cancer and are not originally from each individual patient the treatment will become readily accessible. In the mean time, the treatment is very difficult to access and if approved may be the most expensive cancer drug available. A Citigroup analyst recently estimated that it may cost upwards of $500,000 per patient for the one time treatment. As research continues doctors are waiting for what may be one of the biggest breakthroughs in the history of modern medicine.