In December, 2013, the journal Science nervously named cancer immunotherapy as their “Breakthrough of the Year.” This newfound ability to harness the immune system to combat tumors was beginning to demonstrate enormous promise, but, to cautious scientists the breakthrough label still felt a little premature.
“Were we irresponsible to label as a breakthrough a strategy that has touched a tiny fraction of cancer patients and helped only some of them?” asked one of the journal’s authors.
“A lot has changed since then,” said Thomas Gajewski, MD, PhD, professor in the Ben May Department of Cancer Research at the University of Chicago, who specializes in the care of patients with advanced melanoma, one of the first targets for immune-based treatments. “We now see these drugs as game changers. They are truly effective in many patients.”
Gajewski and colleagues have organized a day-long cancer immunotherapy symposium for physicians and researchers on Monday, April 6, 2015, at the University of Chicago. The meeting will take a close look at the promise of the evolving therapies, and present ideas on how to overcome hurdles and expand the number of patients who can benefit. It will bring together authorities on the basic biology of these drugs with expert physicians who are transitioning them to clinical use.
Immunotherapies enable the body’s immune system to fight tumors. The drugs sparking the most interest are “checkpoint inhibitors.” These block the proteins that cancer cells use to disarm an immune response. Checkpoint inhibitors are able to “take the brakes off the immune system,” Gajewski said, allowing T cells, potent anti-cancer warriors, to attack and destroy tumor cells.
Three of these inhibitors have been approved in the U.S., all for advanced melanoma. All three—ipilimumab, nivolumab and pembrolizumab, marketed as Yervoy®, Opdivo® and Keytruda®—are being tested as a treatment for many other cancers.
On March 4, 2015, the Food and Drug Administration approved nivolumab for patients with advanced (metastatic) squamous non-small cell lung cancer. Lung cancer is the leading cause of cancer death in the United States.
Even though they are still considered experimental for most cancers, “they may already be the most active single cancer therapeutics we have,” Gajewski said. “That’s why we moved this symposium from a lecture hall to an auditorium that seats almost 500 people.”
The University of Chicago has multiple checkpoint inhibitor clinical trials underway, including breast, bladder, lung, mesothelioma, head and neck cancer, and others.
The next step is learning “how to combine these drugs,” Gajewski said. “We want to find synergies, ways to go after two targets at once, to get the maximum effect out of each therapy.”
Another immune-based approach, focused on B-cell leukemias, involves extracting large numbers of a patient’s T cells and genetically altering them outside the body. This process involves inserting a “chimeric antigen receptor (CAR),” a protein that binds to a cell-surface marker called CD19, found on many leukemic cells. When caregivers infuse the CAR T cells back into the patient, they continue to multiply in the body and attack cells displaying the target.
Both approaches have produced high response rates, durable remissions, and, in some cases, significant immune-mediated side effects. These require close monitoring. Early detection and aggressive treatment can reduce immune-mediated complications.
These agents are also quite expensive. At $30,000 per injection, a typical course of Yervoy therapy costs $120,000. Opdivo runs about $140,000 for a year of therapy and Keytruda $150,000. Estimated cost just for the T-cell expansion necessary for CAR therapies ranges from $25,000 to $50,000 per patient. An entire course of treatment could cost an estimated $300,000.
The symposium’s keynote speaker will be James Allison, MD, head of immunology at the University of Texas MD Anderson Cancer Center in Houston, a pioneer in the field. In the mid-1990s, Allison discovered the first checkpoint inhibitor, a finding that paved the way for the development of Bristol-Myers’s ipilimumab, the first drug ever shown to improve survival in patients with advanced melanoma. He will speak on “Immune Checkpoint Blockade in Cancer Therapy.”
Additional speakers include:
- Lisa M Coussens, PhD, Oregon Health & Science University, “Inflammation and Cancer: Reprogramming the Immune Microenvironment as an Anti-Cancer Therapeutic Strategy”
- Thomas F Gajewski, MD, PhD, the University of Chicago, “Molecular Mechanisms of the T Cell-Inflamed Tumor Microenvironment”
- Nicholas P Restifo, MD, National Cancer Institute, Center for Cancer Research, “Developing Curative Cancer Treatments Using Adoptive Cell Transfer-Based Immunotherapies”
- Antoni Ribas, MD, PhD, University of California, Los Angeles, “T Cell and Melanoma Cell Interactions Leading to Response with PD-1 Blockade”
- Alexander Rudensky, PhD, Memorial Sloan Kettering Cancer Center, “Regulatory T Cells and Cancer”
- Michel Sadelain, MD, PhD, Memorial Sloan Kettering Cancer Center, “CAR T-Cell Therapy and the Promise of T-Cell Engineering”
- Robert D Schreiber, PhD, Washington University School of Medicine, “Personalizing Cancer Immunotherapy”
- Melody A. Swartz, PhD, the University of Chicago, “Tumor-Associated Lymphatic Vessels Modulate the Stromal Microenvironment to Promote Tumor Invasion”
The symposium is sponsored by the Ben May Department for Cancer Research at the University of Chicago, the University of Chicago Medicine Comprehensive Cancer Center, the Institute for Translational Medicine and the Committee on Cancer Biology at the University of Chicago, AbbVie, and Ronald Harvey, PhD.
The Cancer Immunotherapy symposium runs from 8:15 AM to 5:00 PM, Monday, April 6, 2015, in the Performance Hall at the University of Chicago’s Reva and David Logan Center for the Arts, 915 East 60th Street Chicago, Illinois 60637.
To register for the symposium, or for more information, visit benmay.uchicago.edu/event/symposium2015.