Today’s vaccines are more nuanced than in years past — no longer seen simply as a way to stop infectious disease. Rather, the treatments in the pipeline today can enhance the body’s own immune system to fight cancer as well as infections that threaten people already diagnosed with cancer.
Researchers hope combining vaccines with other therapies will eradicate cancer.
The year 2012 was notable for progress in this realm. Two vaccines designed and developed at City of Hope now are being evaluated in City of Hope patients.
One vaccine, called CMVPepVax, was designed to help protect patients from complications of cytomegalovirus, or CMV, a common virus that infects most adults by the time they’re 40. Once the virus is present in the body, it’s there to stay.
Though the virus normally causes few symptoms in healthy people, it can be life-threatening to those with compromised immune systems. That includes cancer patients undergoing bone marrow transplants to rid themselves of leukemia and lymphoma.
“Many of the patients are at extreme risk for this infection, which can extend their convalescence at minimum, possibly leading to death in some cases,” says Don J. Diamond, Ph.D., director of the Division of Translational Vaccine Research and the Tim Nesvig Lymphoma Research Fellow at City of Hope. “If successful, this prototype could be valuable for the 65,000 people undergoing transplants annually worldwide.”
Because City of Hope performs hundreds of bone marrow transplant procedures each year, such a vaccine is of critical interest to doctors and researchers here.
In a study conducted at City of Hope, the CMV vaccine was found to be safe and effective at eliciting immunity to the virus in phase I testing in healthy volunteers. Phase I clinical trials are conducted in a small number of human subjects. They’re meant to assess safety, establish dosages and find potential side effects.
The vaccine, developed by Diamond, is now being evaluated in a pilot trial in City of Hope leukemia and lymphoma patients undergoing stem cell transplantation. Pending success of the pilot trial, researchers aim to start a larger, multicenter study.
The other vaccine of note in 2012 is considerably different, relying on a treatment strategy known as immunotherapy.
Diamond offers some context: "The progress for long-term cures for advanced cancer patients has been painfully slow. Chemotherapy in all of its forms has extended lives, though often exacting a heavy toll on the general health of the patient. Unfortunately, the improvements are often fleeting, and patients resume their disease course.”
But he points to what he calls “a bright departure” from that current state of affairs — immunotherapy.
“Harnessing the immune system to attack one’s own cancer, driving it into remission, and possibly eliminating any vestige of its existence is the goal,” Diamond says. “There are newly discovered therapies that succeed where chemotherapy has failed.”
In line with that optimism is a vaccine that was developed at City of Hope, called MVA-p53. The vaccine has been shown to protect mice from a variety of cancers ranging from breast, colon and pancreas tumors. The U.S. Food and Drug Administration approved City of Hope's use of the vaccine in 2011 in heavily pretreated patients living with gastrointestinal cancers, helping them defeat colorectal, stomach or pancreatic tumors.
Developed by Diamond and Joshua D.I. Ellenhorn, M.D., now at Cedars-Sinai Medical Center, the vaccine entered phase I testing in early 2012.
If MVA-p53 clears the phase I safety trial, and researchers expect it to do so, the vaccine will enter phase II testing. That type of study is conducted among more people and is intended to prove that a drug is effective and to further establish its safety.
“One of our goals is to combine the vaccine with one of the new wonder drugs that have shown activity in patients that were once thought to be incurable or only have a few months to live,” Diamond says. “We strongly feel that the combined regimen may even extend life longer than what the FDA-approved Ipilimumab (from Bristol-Myers Squibb) and the experimental drug MDX 1106 (also from Bristol-Myers Squibb) have attained."