December 29, 2012 | by Tami Dennis
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.
The year 2012 was notable for progress in this realm, with two vaccines designed and developed at City of Hope now being evaluated in City of Hope patients.
John A. Zaia, M.D., chair of the Department of Virology, cites these two vaccines as prime examples of the year’s significant advances in vaccine therapy. The vaccines are the result of what is known as “translational research,” beginning as laboratory discoveries at City of Hope and later being developed into a product with the potential to save lives worldwide. Today, this type of research is known as “bench to bedside.”
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, such as cancer patients undergoing hematopoietic cell 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. “If successful, this prototype could be valuable for the 65,000 people undergoing transplants annually worldwide.”
Because the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope conducts hundreds of hematopoietic cell transplants annually, such a vaccine is of critical interest to doctors and researchers here.
In a study conducted at City of Hope and led by Zaia, the CMV vaccine was found to be safe and effective at eliciting T cell immunity in Phase 1 testing in healthy volunteers. Phase 1 trials are conducted in a small number of human subjects and are meant to assess safety, establish dosages and identify 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. Success is defined as substitution of the vaccine for one or more courses of toxic chemicals known as antivirals; such chemicals are so harsh that they often spawn infections that can prove deadly themselves.
Corinna La Rosa, Ph.D., an associate research professor in the Division of Translational Vaccine Research, conducted the immunologic analysis of CMVPepVax; Ryotaro Nakamura, M.D., an associate professor in the Department of Hematology & Hematopoietic Cell Transplantation, is the lead investigator monitoring the study in stem cell transplantation patients.
Stephen J. Forman, M.D., chair of the Department of Hematology & Hematopoietic Cell Transplantation, is a longtime advocate of milder treatments for CMV infection -- and has committed his departmental physicians, nursing staff and many others to assist Nakamura, Diamond says. Also deserving credit are the National Cancer Institute, which has provided more than $10 million in funding to the program, and drug manufacturer Pfizer, which has provided a key component of the vaccine to trial investigators, Diamond adds.
Pending success of the pilot trial, the NCI will provide a fresh lot of vaccine to support a large multi-center Phase 2 study jointly with the University of Minnesota Comprehensive Cancer Center. The pilot trial is listed in the clinicaltrials.gov website.
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. Its platform is a weakened virus that ordinarily is used by the U.S. government as a preventive vaccine for a potential terrorist release of smallpox.
The vaccine has been shown to protect mice from a variety of cancers ranging from breast, colon, and pancreas tumors. The FDA approved City of Hope's use of the vaccine in 2011 in heavily pre-treated 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 1 testing in early 2012.
Vincent Chung, M.D., a clinical associate professor in the Department of Medical Oncology & Therapeutics Research, is leading the first-in-humans trial. Nicola Hardwick, Ph.D., in the Division of Translational Vaccine Research is the research fellow analyzing patient’s immunity after they were given the vaccine. Many others from Medical Oncology and Therapeutics Research and the Phase 1 Unit are also contributing, Diamond points out.
The NCI supported much of the formative aspects of the vaccine development, though City of Hope played a large role when government coffers dried up. The trial is listed in the clinicaltrials.gov website.
If MVA-p53 clears the Phase 1 safety trial, and researchers expect it to do so, the vaccine will enter Phase 2 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."
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