The Johns Hopkins Kimmel Cancer Center in Baltimore has always been a leader in translational research—laboratory discoveries that improve the lives of patients. One of the many successes has been a pancreas cancer vaccine.
The vaccine was developed more than decade ago in the laboratory by scientist and pancreas cancer program director Elizabeth Jaffee, M.D., a leading cancer immunology and pancreas cancer expert, and taken to patients by leading pancreas cancer clinician Daniel Laheru, M.D. Jaffee and Laheru are co-directors of the Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care.
To make vaccine therapy a reality, Jaffee became an expert in U.S. Food and Drug Administration regulations and vaccine manufacturing, and opened a GMP (good manufacturing practices) facility at the cancer center to make the vaccine. She also has recruited and trained other specialists including Jen Uram, Ph.D., who have become expert in working with the FDA, National Institutes of Health and industry.
A Popular and Unique Potential Therapy
Clinic coordinator Susan Sartorious receives more than 60 inquiries a month from patients hoping to receive the pancreas cancer vaccine or participate in other immunotherapy-focused studies. “There is no other cancer center doing this kind of work,” says Lei Zheng, M.D., who is working with Jaffee on the pancreas cancer vaccine. The Skip Viragh Center has allowed Jaffee, Laheru and team to make these groundbreaking treatment advances available to patients throughout the U.S. and around the world.
Zheng is among the group of bright, young scientists supported through Skip Viragh’s legacy. He is working with Jaffee in the laboratory to optimize the effects of her pioneering pancreas cancer vaccine by better understanding the tumor environment. This support has been key to her research and was instrumental in her studies to decipher precisely how pancreas cancer and the immune system work together to allow the disease to progress.
Additional Vaccine Research
Activating the immune system to recognize pancreas cancer cells and simultaneously suppress mechanisms co-opted by tumor cells to shut down an immune response is a complex and delicate process. Jaffee and team have studied timing of vaccination as well as combining the vaccine with drug and radiation therapies to boost its tumor-killing capabilities. More recently, with the help of Viragh Scholar Dung Le, M.D., Jaffee has developed an approach that combines the vaccine with a drug treatment that targets mesothelin, a protein on the surface of pancreas tumor cells believed to contribute to the growth and spread of the cancer. Ralph Hruban, M.D., pathologist and director of the Sol Goldman Pancreatic Cancer Research Center, and chief of pathology at the Johns Hopkins University School of Medicine, found mesothelin in high levels on the surface of pancreatic cancer cells, and Jaffee and Le believe the protein helps pancreatic cancer cells to grow and spread.
In other attempts to boost the effectiveness of the pancreas cancer vaccine, Zheng is focusing on connective tissue cells called stromal cells in the pancreas, and developing methods to attract cancer-fighting immune cells into tumors while suppressing and bypassing barriers that prevent them from attacking cancer cells.
He is among the first to recognize that stromal cells actively drive the growth and spread of pancreas cancer cells. In this newer area of research, he is just beginning to decipher the molecular and cellular mechanisms they use.
Stromal cells are not prevalent in the normal pancreas, but in cancer, Zheng suspects that stromal cells become engaged as a result of inflammation or some other injury to the pancreas. This injury may be an early event in cancer development attracting stromal cells as well as immune cells to the organ. Cancer cells somehow take advantage of the changes by creating a protective environment that allows them to grow. He hopes his novel research will lead to ways to target and inhibit these changes and create an environment less hospitable to cancer.
Other new work includes the use of peptides to create the first vaccines individualized to the unique molecular characteristics of each patient’s cancer and, as a result, improve the response against pancreas cancer. Peptides are the building blocks of proteins and are a “table of contents” of sorts displayed on the cell surface to reflect the internal molecular structure of the cell. Vaccines could use peptides to prime immune cells to recognize when something is not right within a cell, such as with cancer. Researchers are studying whether identifying peptides that mark each patient’s specific tumor cells, incorporating these peptides in the pancreas cancer vaccine, and then combining them with immune-modulating drugs that release cancer’s grip on immune cells, could boost the immune response against cancer cells.
Jaffee, Laheru, Le, Zheng, and others are testing various versions of the vaccine, built from pancreatic cancer cells that have been rendered dormant with radiation and engineered to recruit immune cells to track and attack malignant cells anywhere in the body and to continue to do it indefinitely. They are making tweaks in timing of vaccination and changes to its composition and delivery that they hope will boost its cancer-killing capabilities and make the vaccine a treatment option for many more patients. One of their new approaches is to give the vaccine before surgery.
Jaffee’s ultimate goal is to use these discoveries to develop a vaccine that prevents pancreas cancer. She and her team are focused on deciphering the specific information the immune system needs to immediately recognize early changes in cells that occur before cancer develops.
Early Clinical Trial Results
Early laboratory findings resulted in major breakthroughs and have gained national attention and recognition from the National Cancer Institute’s (NCI) prevention program. As a result of Jaffee’s work, the NCI is sponsoring a joint workshop that will bring together leading experts in disease prevention and cancer immunology.
Jaffee says, “Vaccines have been used to prevent many infectious diseases. It only makes sense to harness this power for cancer, and I think we may now have the technology and capability to make it happen.”
Early results of the pancreas cancer vaccine clinical trials look promising:
- In 2005, data showed that two years into a study of 60 patients, 88 percent had survived one year, and 76 percent had survived two years
- In 2007, the researchers reported that three years into the study, the average survival time was 26.8 months.
Current studies are aimed at developing personalized immunotherapy together with contemporary chemotherapy and radiation after surgery.
Ongoing studies of the vaccine are testing its abilities in conjunction with other therapies.