Cancer pancreatic vaccine

Johns Hopkins University researcher Dr. Elizabeth Jaffee has spent the past decade developing a vaccine that offers hope for people facing pancreatic cancer. Employing a strategy known as immunotherapy, Dr. Jaffee and colleagues are using a patient's own genes as weapons to destroy--and possibly prevent recurrence of--one of the deadliest of cancers. While childhood vaccines are normally thought of as a means to prevent disease such as chickenpox or influenza, cancer vaccines are used in conjunction with other therapies to help battle the disease.

"Typically, we think of vaccines as prevention. We use the viral or bacterial agent as the immunogen which generates an immune response," Dr. Jaffee, a professor of oncology, pathology, immunology, and cell and molecular medicine at the Johns Hopkins School of Medicine, tells the Post. "With the pancreatic cancer vaccine, we are talking about treatment because we do not yet know what causes pancreatic cancer. In pancreatic cancer, we have to wait until the malignant cell is present and then use that cell as a source of immunogen."

To ignite the battle between the immune system and the cancer, Hopkins researchers extract cells from a patient's tumor removed during surgery. They then grow the cancerous cells in the laboratory, inserting into those cells a gene that produces natural immune-stimulating molecules called cytokines, a family of proteins that helps orchestrate immune response to different agents, such as infection. The genetically modified cells are irradiated to prevent them from reproducing, then injected into the patient. The cells produce the cytokine--called granulocyte-macrophage colony-stimulating factor, or GM-CSF--which alerts the immune system to recognize tumor antigens as a potential infection and to attack cells bearing those antigens.

To date, the results have been promising.

"In three patients at the highest dose levels, we found that those patients demonstrated not only an immune response but prolonged disease-free survival," says Dr. Jaffee of the Phase I trial on a small group of patients. "They have remained disease-free for almost 4 1/2 years after diagnosis. For pancreatic cancer, this outcome is very good."

The team is now enrolling patients for a Phase II study. To qualify, patients are first treated with conventional therapy (surgery, radiation and chemotherapy) to rid the body of the bulk of the cancer. Vaccines are then employed to stimulate immune response to find and destroy remaining cancer cells.

Genetically engineered vaccines could be used to `mop up' microscopic cancer cells left behind following surgery, chemotherapy and radiation," Dr. Jaffee says. "We need to find the combination of these treatments that will afford the patient the best chance of survival."

Researchers have launched the second phase of their clinical trials, which is presently open to enrollment. The first phase boasted 60 patients.

"In our protocols, we believe that the vaccine works better when combined with other modalities--with surgery first," says Dr. Jaffee. "They have to be surgical candidates for the procedure here at Johns Hopkins be cause we need to get the tumor to process for one of the immune-monitoring studies. We give them the vaccine about eight weeks later, then send them on to adjuvant chemotherapy and radiation, After that, they get three more vaccinations."

Identifying the genes behind pancreatic cancer is key to discovering a cure. Fellow Johns Hopkins scientist Dr. Ralph Hruban, who directs the National Familial Pancreatic Tumor Registry, is one of the leading researchers into the genetics of pancreatic cancer in the world. And Dr. Hruban's work has been greatly aided by the more than 1,300 Post readers who have responded to the Pancreatic Cancer Survey (page 43), which is promptly sent to Dr. Hruban and another key researcher studying the genetics of the disease. Studying families where a genetic predisposition to pancreatic cancer appears to be present helps researchers isolate genes and develop new therapies, such as Dr. Jaffee's, against the deadly disease.

"Their work is critical," comments Dr. Jaffee, who lost an uncle to pancreatic cancer early in life--a key event that triggered her interest in finding better therapies for the disease. "People doing gene discovery, as well as others in the field, are coming out with potential targets on a regular basis. Sooner or later we are really going to get a handle on what makes a normal cell become a pancreatic cancer. If you know that, you can start to look at pathways to inhibit that process. I think it is a very hopeful time."

If readers are interested in learning more about the vaccine study, they can contact Barbara Biedrzycki, nurse practitioner and program coordinator for the Johns Hopkins Oncology Center Cancer Vaccine and Immunotherapy Program, at 410-614-6894 or by e-mail (biedrba@jhmi.edu).