DISSOLUTION OF CANCER CLUB WANTED
If you are part of the “cancer club,” it means that you are personally familiar with the devastation cancer causes. Far too many of us are members, whether it is through supporting loved ones with cancer or enduring and persevering with it ourselves.
It has long been the goal of physicians and researchers who specialize in cancer treatment to harness the built-in power of a patient’s own immune system to fight this dreaded disease. The ability to successfully do so means more effective and less toxic treatments for cancer patients.
Monoclonal antibody (mAb) therapies that bind to cancer cell-specific proteins and induce an immunological response were the first treatments that achieved the goal. Since the approval of the first mAb cancer therapeutics in the late 1990s, cancer-specific immunotherapy has come a long way. This week and next, we will take a look at some of the hottest new cancer-fighting immunotherapies in development.
BUILDING BETTER WARRIORS
Circulating throughout your body is an army of stealth warriors. When they do their job correctly, you do not even know they are there or appreciate the perils they save you from. These warriors are known as T-cells—a specific type of white blood cell that seeks and destroys virus-infected cells and tumor cells.
Each T-cell has a unique receptor protein on its surface that recognizes a specific target protein. As T-cells are completing their development, receptors that recognize self (proteins on the surface of the host’s own tissue) are destroyed to prevent autoimmune disorders. This protection against autoimmunity, however, means some tumor cells inevitably escape detection since tumor cells are simply one’s own cells dividing too rapidly or too frequently. Often, it is not until later in the cancer cells’ development that a tumor antigen appears, enabling it to be targeted by the immune system.
Today, scientists are engineering T-cells to recognize a specific tumor antigen. T-cells are removed from the patient’s blood. Researchers use viruses (stripped of their ability to cause illness but retain their capacity to integrate into cells’ DNA) to deliver genetic material to produce a modified T-cell receptor. This modified T-cell is called a chimeric antigen receptor T-cells (CART) which is able to recognize proteins on the surface of the patient’s tumor. CART cells are then multiplied in the lab and infused back into the patient’s blood, where they ferret out and destroy tumor cells.
IN THE CLINIC: LIVING DRUGS
CART therapy originated from research done by Dr. Carl June at the University of Pennsylvania, and subsequently was licensed and developed by Novartis. Other companies pursuing CART include Juno Therapeutics, Kite Pharma, Cellectis, and Celgene.
Although still in early-stage clinical trials, initial results offer much hope: in several leukemia patients, cancer cells were reduced to undetectable levels!
One potentially troubling side effect was observed: in some patients, infusion of the newly engineered T-cells induced a strong inflammatory reaction causing serious symptoms such as fever and precipitous drop in blood pressure. However, these symptoms were successfully managed with drugs already approved to treat inflammatory conditions.
If engineered T-cells continue to live up to the hype, we can look forward to what some have termed a “living drug”—cancer-fighting cells that will persist and multiply in a patient’s body until the tumor is destroyed.
In non-humans, a few cancers are transmissible among the same species; Sticker’s sarcomas in dogs and devil facial tumor disease in Tasmanian devils.
TERM OF THE WEEK: IMMUNOTHERAPY
Immunotherapy: therapies that harness the power of a patient’s immune system to combat a disease.
Emily Burke, PhD has worked in biopharma for 20 years, gaining science writing experience at The Scripps Research Institute and Ionis Pharmaceuticals. As a Ph.D. molecular biologist, she is passionate about advancing the public’s understanding of science. In addition to being a self-proclaimed “science geek,” she is regularly asked to speak at international scientific meetings. When not teaching and writing the WEEKLY for Biotech Primer, Dr. Burke swims with her swim club and performs regularly on the improv circuit in San Diego.