Gajewski, professor in the Departments of Pathology, Medicine and the Ben May Cancer Institute at the University of Chicago and director of the immunology and cancer program at the University of Chicago Medicine, is a pioneer in the field of cancer immunotherapy, one of the most promising approaches to cancer treatment in decades.
Cancer immunotherapy exploits the power and specificity of the immune system to fight cancer. First tested in melanoma, immunotherapy has led to complete remissions in many cancer types, often with limited side effects.
“The Outstanding Investigator Award (OIA) pulls together a number of separate but related projects from our lab and blends them into one massive, cohesive undertaking,” Gajewski said. Such funding is necessary for our lab and many others to make continual progress toward preventing and treating cancer using the host immune system. It inspires us to be even more aggressive, to move the field forward as broadly and quickly as we can.”
The NCI’s Outstanding Investigator Awards support scientists who demonstrate remarkable productivity in cancer research. By providing seven years of financial stability, these awards encourage investigators to take on long-term projects with significant potential.
“It allows funded investigators to take greater risks and be more adventurous in their research,” Gajewski said. “We can now focus entirely on doing the work and worry less about writing grant applications, making us more productive and efficient.”
Gajewski’s team studies new ways to overcome a tumor’s ability to resist immunotherapy, with a focus on drugs that help the immune system, especially T cells, gain access to tumor sites.
Their approach is multidimensional. “We have treated a large number of melanoma patients using immunotherapies,” he said, “and we now have a great deal of data about the interactions between a patient’s tumors and his or her immune system. We know who responded to treatment and who didn’t. Now we’re cataloguing genetic clues that correlate with response versus resistance. This not only should help us predict who is most likely to benefit, but more importantly identify new therapies to overcome resistance and expand efficacy.”
They are also looking at connections between the gut microbiota – the microbes that live in a patient’s digestive tract – and the immune system’s response to cancer. In 2015, Gajewski’s laboratory showed that a particular strain of bacteria in the digestive tracts of mice could stimulate the immune system to attack tumor cells. They are now refining this approach and analyzing a large cohort of human samples.
A third element is investigation of a protein complex known as STING – short for STimulator of INterferon Genes – which plays a crucial role in detecting cells in which the DNA is in the wrong place, within the cell but outside the nucleus. In 2014, Gajewski’s laboratory showed how the STING pathway signals the body’s innate immune system to attack such tumor cells. “We are now working with a small molecule drug that appears to trigger this response when injected directly into a tumor,” he said. Clinical testing is underway.
“So much of this work is collaborative,” Gajewski said. “We have a lot of faculty and trainees working together to translate these basic observations into systems we can test in the clinic. A major next step is to integrate the various components.”
Being awarded an OIA is “a significant honor and a pleasant surprise,” Gajewski added. “It celebrates and builds on a long research path, made possible by public as well as private support.”