Sharla A. Paul
When telling the story of immunotherapy and cancer and how the two battle it out, it’s awfully challenging not to pull out the old A Tale of Two Cities cliché. Because everyone agrees: It is the best of times in cancer research and treatment.
Over the past five years, the standard of care for treatment of many cancers has made a decided shift toward marshalling a patient’s own immune system to attack the disease. The full spectrum of immunotherapies available are administered at the University of Chicago Medicine Comprehensive Cancer Center.
Researchers here are shaping the future of cancer treatment from every corner. Work on the role of the human microbiome has entered a phase 1 clinical trial. The search for biomarkers, also in clinical trials, is designed to better target patients who will respond to specific therapies. Precisely engineered molecules, still in the first stages of development, could enable therapies to be delivered directly to tumors, rather than systemically, reducing toxic or autoimmune side effects. A new understanding of the basic biology of the lymphatic system has the potential, further down the road, to bring immunotherapies to more patients.
This work, and far more, comes out of the network of labs that constitute the Comprehensive Cancer Center, one of only two National Cancer Institute–designated cancer centers in Illinois. Founded on UChicago interdisciplinary principles, the Cancer Center brings together faculty members from UChicago Medicine, the Biological Sciences Division and the Physical Sciences Division. Some are also members of the two-year-old Microbiome Center and the seven-year-old Institute for Molecular Engineering. With so many minds at work, the effort is moving fast and findings rapidly build upon each other.
And yet, for so many cancer patients still, it is the worst of times.
Immunotherapy is available for only some types of cancer. In an editorial in STAT in 2017, two oncologists at Oregon Health & Science University estimated that “two-thirds (68.8 percent) of Americans predicted to die of cancer will die of one that currently has no FDA-approved immunotherapy options.” Many patients’ immune systems do not respond to treatment. Some patients experience toxic side effects that may end the therapy or be fatal. Advanced clinical trials can fail; UChicago was part of one multinational phase 3 trial that failed this past year. The cost of treatment can be in the hundreds of thousands of dollars, and insurance coverage is not certain. In 2013 Science heralded immunotherapy as the Breakthrough of the Year. By spring 2016 the cover of Time called immunotherapy clinical trials—the main means of access to the therapy—“brutally selective, hugely expensive, lifesaving.”
Wisdom, foolishness; belief, incredulity; light, darkness; hope, despair. Cancer still beats us too much of the time. For the UChicago Medicine physician-clinician making rounds and researching treatments, cancer will also inspire redoubled efforts to beat it back.
And so we enter our story, well under way.
The mice have played their parts. A promising immunotherapy has left the lab. Late-stage cancer patients enroll in clinical trials under the watchful eyes of the nation’s oncologists. These physicians await whichever therapies will achieve endpoints, gain FDA approval and help care for their long lists of patients: those whose disease they have barely staved off for years, and those whom the oncologists hope not to need to tell that they have an advanced case and may not have long to live.
In the early morning hours of June 4, 2018, two of our main characters are onstage among a group of eight. It’s dark, and the crowd is swaying and whooping.
“Baby, don’t you know it’s a damn crying shame?” Buddy Guy—yes, that Buddy Guy—growls into his microphone.
To Guy’s right, the lead guitarist, an unassuming white man in glasses, jeans and a maroon polo, grinds out an accompanying riff. The oncological twittersphere lights up.
“It’s midnight at #ASCO and do you know where some of the world’s most famous #immunotherapists are?” comes the tweet from Bernard A. Fox, a cancer immunotherapist and academic researcher from Oregon. It is the end of day three of the annual meeting of the American Society of Clinical Oncology in Chicago, and some of the world’s most famous immunotherapists are up on stage with Buddy Guy.
The unassuming lead guitarist? Thomas Gajewski, AB’84, PhD’89, MD’91, the AbbVie Foundation Professor of Cancer Immunotherapy.
The grinning dark-haired man, slightly behind Gajewski and Guy, trumpet at the ready? Jason Luke, assistant professor of medicine.
It was Gajewski’s work on T cells in cancer that led Luke to join UChicago in 2014 from the Dana-Farber Cancer Institute and the Harvard Medical School faculty. Luke works with Gajewski to manage clinical trials of novel immunotherapies, including new combinations of drugs, and just opened a phase 3 melanoma trial for stage 2 disease.
Gajewski, like Luke, specializes in melanoma, but the trials also seek to bring immunotherapies to patients with other types of cancer tumors. They have built a “bIObank,” or bank of ImmunoOncology samples, of patients’ tissues, tumor biopsies and complex blood tests, which are packed with information about patients’ immune responses to the therapies—or, most likely, lack thereof. Information from the bIObank feeds back into the basic science research conducted in Gajewski’s lab and by other researchers, including those at the Institute for Molecular Engineering.
The rest of the musicians performing with Guy are renowned oncologists from cancer centers and academic institutions across the country. Sax, trombone, drums, another guitar, a harmonica, vocals—to the crowd recording the scene with raised smartphones, these are the stars of their field.
“You know it’s a crying shame,” Guy sang, bemoaning a two-timing woman while Gajewski’s guitar whines.
For Luke, the crying shame is the two-timing immune system.
He and his bandmates named themselves the CheckPoints after a critical mechanism in the human body’s immune response. The basic idea is as follows: The body depends on the immune system generally to remain in default mode, recognizing normal cells and leaving them be. Checkpoints are the proteins on cells that keep the immune system in check in the presence of healthy cells.