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Cancer cells of the human colon whose nuclei are stained red and the E-cadherin protein stained green. Credit: Urbain Weyemi, Christophe E. Redon, William M. Bonner. NCI Cancer Research Center
A new colorectal cancer vaccine showed positive results in the Phase 1 clinical trial, demonstrating that the approach was safe. Treated patients showed no signs of serious adverse events and samples of their blood contained markers of immune activation – an early indication that the vaccine could activate immune cells to fight colorectal tumors and metastases . Other tests to determine if the vaccine is effective in slowing down tumor growth are forthcoming.
The results were published in the Journal of Cancer Immunotherapy.
Colon cancer, particularly among young people, is increasing and is currently the second leading cause of cancer deaths in the United States and around the world. Surgery can cure the disease in many patients, but the prognosis is bad for those who have recurred. If it's found to be effective in large-scale trials, the vaccine, developed by researchers at Jefferson (University of Philadelphia and Thomas Jefferson University), could result in the body's immune system. patient to attack colon cancer already present before the operation.
"It is urgent to understand what is driving the growth of colorectal cancer and to use that knowledge to develop new therapies. This pivotal study provides one of the first evidences that it is possible to safely direct the patient's immune system towards the search for and the destruction of this type of cancer. This is a milestone made possible by the scientists and clinicians of our colorectal cancer team working in synchrony, "said Karen E. Knudsen, Ph.D., Executive Vice President of Cancer Services. Oncology and director of the Sidney Kimmel Cancer Center – Jefferson Health.
In previous preclinical work on mice, Jefferson researchers showed how the design of their vaccine worked. Antitumour vaccines have always been developed to fight cancer. As they come from normal cells, cancer cells share almost all the same molecules, which prevents the immune system from differentiating normal cells from cancer cells. Tumor antigens are molecules that the immune system can recognize as different from normal. In colorectal cancer, one of these molecules, GUCY2C, was identified by Scott Waldman, MD, PhD, Samuel M.V. Professor Hamilton and director of the gastrointestinal cancer control program at the Sidney Kimmel Cancer Center – Jefferson Health.
The vaccine developed by the first author, Adam Snook, PhD, an badistant professor in the Department of Pharmacology and Experimental Therapeutics, Dr. Waldman and others, works by activating the immune system against the GUCY2C molecule. By joining the molecule GUCY2C to a molecule that stimulates the immune response called PADRE, and loading it into an adenoviral vector, researchers have developed a vaccine that can specifically target colon cancer.
The current clinical trial included 10 patients with stage I or II colon cancer. Patients were dosed and returned for blood sampling 30, 90 and 180 days after vaccination. Patients experienced some discomfort at the injection site, but did not report any serious side effects of the vaccine. Blood samples showed the activation of "killer T cells", the type of immune cells that researchers had been waiting for. These killer T cells are responsible for the discovery and destruction of cancerous colon cells responsible for the return of cancer.
"We are preparing for a Phase II study that will begin recruiting patients this fall," said Dr. Snook. "We used the lessons learned from the first study to modify the vaccine to make it even more effective."
Since the start of the trial, researchers have discovered that cancers other than colorectal cancer also express GUCY2C, including cancers of the stomach, esophagus and pancreas. These are actually some of the most deadly cancers. In fact, with colorectal cancer, these four types of cancer are responsible for 20% of cancer-related deaths.
"The goal of the study that will begin this fall is to show that version 2.0 of the vaccine is even better and that it could benefit a much larger group of the overall population of patients with cancer, "says Dr. Snook.
This article has been republished from documents provided by the Sidney Kimmel Cancer Center – Jefferson Health. Note: Content may have changed for length and content. For more information, please contact the cited source.
Reference: Adam E. Snook, et al. "Shared tolerance allows safe T-cell responses induced by the Ad5-GUCY2C-PADRE vaccine in patients with colon cancer. Journal of Cancer Immunotherapyr (2019) DOI: 10.1186 / s40425-019-0576-2
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