Vaccines may make war on cancer personal

In the near future, physicians may treat some cancer patients with personalized vaccines that spur their immune systems to attack malignant tumors. New research led by scientists at Washington University School of Medicine in St. Louis has brought the approach one step closer to reality.

Like flu vaccines, cancer vaccines in development are designed to alert the immune system to be on the lookout for dangerous invaders. But instead of preparing the immune system for potential pathogen attacks, the vaccines will help key immune cells recognize the unique features of cancer cells already present in the body.

In the new study, which appears Nov. 27 in an issue of Nature focused on cancer and the immune system, scientists tested investigational vaccines in computer simulations, cell cultures and animal models. The results showed that the vaccines could enable the immune system to destroy or drive into remission a significant number of tumors. For example, the vaccines cured nearly 90 percent of mice with an advanced form of muscle cancer.

“This is strong evidence that personalized cancer vaccines can be very effective cancer therapies and should be applied to human cancer now,” said senior author Robert Schreiber, PhD, the Alumni Professor of Pathology and Immunology and director of the university’s Center for Human Immunology and Immunotherapy Programs.

Scientists at the Siteman Cancer Center at Washington University and Barnes-Jewish Hospital are in the process of using these vaccines against many different types of cancers including breast, brain, lung, and head and neck cancers. The most advanced of these studies, led by Gerald Linette, MD, PhD, and Beatriz Carreno, PhD, is evaluating personalized cancer vaccines in patients with metastatic melanoma.

The vaccines are being developed in collaboration with scientists at The Genome Institute at Washington University.

Creating a personalized vaccine begins with samples of DNA from a patient’s tumor and normal tissue. Researchers at The Genome Institute sequence the DNA to identify mutant cancer genes that make versions of proteins found only in the tumor cells. Then they analyze those proteins to determine which are most likely to be recognized and attacked by T cells. Portions of these proteins are incorporated into a vaccine to be given to a patient.

Years of studying cancer genetics and of the immune system’s interactions with cancer have made the vaccine strategy possible.

The technique was inspired by a therapy scientists call checkpoint blockade. This immune-based cancer treatment, which has been successful against advanced lung and skin cancers in clinical trials, takes advantage of immune T cells that are present in many tumors but have been shut off by cancer cells.

The cancer cells shut off the T cells by activating a safety mechanism called the checkpoint system. This system helps prevent immune cells from attacking the body’s own tissues.

Checkpoint blockade takes the brakes off T cells, unleashing their destructive capabilities on the tumors. But the approach also increases the chances that those same immune cells erroneously will attack healthy tissue, causing serious autoimmune disease.

“We thought it would be safer to find ways to identify the mutated tumor proteins that are the specific targets of the reactivated T cells that attack the tumors,” Schreiber said. “We believe we can incorporate those proteins into vaccines that only unleash the T cells on the tumors, and so far, our tests have been very successful.”

The research was made possible in part by Washington University’s Center for Human Immunology and Immunotherapy Programs, which provides shared laboratory facilities and other support to aid the bench-to-bedside development of immunotherapy research.