Vaccines have been developed to fight the flu, combat chicken pox, and battle Hepatitis B. David Peace is working to add cancer to that list of diseases.
Peace, MD, a member of the University of Illinois Cancer Center and professor of hematology and oncology at the University of Illinois College of Medicine, is conducting basic and translational research in tumor immunology in hopes of developing vaccines to treat numerous cancers, including prostate, kidney and bladder.
The majority of Peace’s research career has been devoted to the immunology field, and during that time he has seen sweeping changes in how cancer can be treated, from the use of checkpoint inhibitors, CAR-T cells, and vaccines, among other modalities. Identifying tumor-specific antigens and developing strategies to elicit tumor-specific T-cell immunity in patients has been a focal point of his studies over the years.
“It’s been fascinating and exciting to watch the emergence of checkpoint inhibitors, as they block the normal proteins on cancer cells and allow T-cells to respond to many different types of tumors,” Peace said. “But I have been interested in trying to figure out how to develop very precisely directed immunotherapy. I have been especially interested in exploiting tissue-specific antigens such as prostate specific antigen (PSA) and prostate specific membrane antigen (PSMA), which can serve as “tumor specific” markers in the right context.”
Throughout his career, Peace has translated his discoveries in the lab into clinical trials. In 2002, he developed and tested a vaccine that boosts the body’s own immune system in an effort to cure prostate cancer. Sponsored by the National Cancer Institute, the vaccine included a carefully selected peptide fragment of PSA, which is produced by cells lining the tubules of the prostate gland, as well as by prostate cancer cells.
During the trial, Peace demonstrated that PSA can be safely exploited therapeutically – to enlist the immune system to target prostate cancer cells for destruction. At the time, his studies showed that the vaccine caused subsets of the immune system’s white blood cells to morph into highly specific killer white blood cells, called cytotoxic T lymphocytes, which selectively destroy tumor cells that express PSA. The trial showed that PSA-specific killers could be generated from not only healthy individuals but patients with advanced prostate tumors.
The vaccine was either injected under the skin, along with a compound that could stimulate the immune system, or delivered intravenously, after being loaded onto dendritic cells, a type of white blood cells that activate the immune system by scavenging antigens, like PSA, and presenting them to T cells, one of the body’s most important defense mechanisms.
“At the time we did this, it was rather shocking to see actual responses in men with advanced disease,” Peace said. “Although it was a small study, about 50 percent of the patients responded to the vaccine. What’s fascinating is that some of those patients are still alive. We selected patients because they were expected to have shortened lives, but some have beaten the odds and are extremely grateful and thankful for the study.”
After discovering that PSMA is expressed on the blood vessels that supply a variety of different tumors, Peace became interested in developing a more universal vaccine that can cripple tumors by targeting their vascular supply. He has explored a series of proteins that are selective markers of tumor blood vessels as potential targets for cell immunotherapy. One particular protein, TEM8 (tumor endothelial marker 8) has shown some success.
“TEM8 contains small peptide fragments that target the immune system and speeds up a targeted response, so we’re keen to marry the two concepts together,” Peace said. The TEM8 protein could be used in a vaccine against not only prostate cancer, but pancreatic, stomach, colon and other cancers.
While cell based therapies such as CAR-T cells offer a powerful, albeit highly expensive, avenue for delivering specific T cell immunity against cancers, simple peptide vaccines properly delivered and amplified may prove equally effective and far less costly, according to Peace.
In the latest trial he is assisting with, Peace is using a combination of a checkpoint inhibitor and the tumor vessel blocking drug Avastin to treat patients with advanced kidney cancer. Conducted through the Big 10 Cancer Research Consortium, the trial has rapidly accrued and “we’ve had favorable results in the response rates we’re seeing,” said Peace, whose work has been extensively published in such periodicals as Journal of Clinical Oncology, Journal for ImmunoTherapy of Cancer, and Clinical and Developmental Immunology.
Peace’s early medical training was strongly influenced by Dr. Thomas Starzl at the University of Pittsburgh. He contemplated a career in transplant surgery, but he ultimately chose to pursue his interests in transplantation and immunology by moving to the Pacific Northwest for a fellowship at Seattle’s Fred Hutchinson Cancer Research Center, under the guidance of Dr. E.D. Thomas, the pioneer of hematopoietic stem cell transplantation.
While at Fred Hutchinson, the majority of Peace’s research was conducted in tumor immunology. At that time there were many creative and exciting things happening in Seattle, he said. It was the early days of T cell therapy, gene cloning, cytokine discovery and monoclonal antibody technology. The technologies, Peace said, were very novel, and extremely promising.
“We thought this new research was going to be able to cure many different diseases and that we finally had our hands on the magic bullet,” he said. “But where were we going with it? I said cancer, and I’ve been working with it ever since.
“There are so many new “precision” drugs that have been introduced over the past decade,” said Peace, who left Seattle in 1992 to join Loyola University of Chicago before moving to UIC in 1997. “We’re seeing an unprecedented acceleration in drug development, and enthusiasm is growing that these are going to be game changers in terms of patient outcomes and the ultimate eradication of cancer. We’re just at the beginning of the effective use of these modalities of therapy.
“It’s truly a great time to be in oncology.”