Duke Researchers Prime Immune System With RNA to Fight Cancer
SEATTLE, WA -- Researchers at Duke University Medical Center reported Saturday that a rare and powerful immune system cell called a dendritic cell, when combined with the genetic instructions from tumor cells, can be trained to attack cancer throughout the body.
The potential therapy, described by Duke immunologist Smita Nair at the first annual meeting of the American Society for Gene Therapy, is the next generation of a cancer vaccine now being tested in cancer patients at Duke. Its ultimate goal is to wipe out cancer cells and then keep the body protected from new cancer growth.
According to Nair, the new therapy has the potential to become a universal cancer vaccine that could be used to fight many types of cancer. Making the vaccine requires white immune cells from a sample of blood and a few cancer cells from which to distill the genetic material RNA.
"In our recent work, we have shown that RNA from tumors, when combined with dendritic cells, can stimulate a powerful response against tumor cells in laboratory experiments," said Nair, a researcher in Duke's Center for Genetic and Cellular Therapies. "This is the next generation of cancer vaccine."
The Duke cancer vaccine harnesses two biological powerhouses: dendritic cells, which seek out foreign tissue and alert the immune system, and RNA, the agent that transfers information from a cell's genome to the protein synthesis machinery of the cell.
Dendritic cells circulate throughout the body, looking for "foreign" protein, such as that produced by invading bacteria. The dendritic cells then "eat" the antigens and display the antigens on their own cell surface. This show of a foreign antigen signals a strong response from immune system fighters known as "killer T" cells, which move out from the spleen and lymph nodes to attack the invader.
Cancer cells produce a variety of atypical proteins, but tumor cells have evolved ways of effectively hiding these proteins from dendritic cells. Because of this, cancer is virtually invisible to the immune system, Nair said.
The Duke researchers, including Dr. Eli Gilboa, research director of the Center for Genetic and Cellular Therapies, surgeon Dr. H. Kim Lyerly, and David Boczkowski, have devised a way to engineer dendritic cells to display tumor antigens. They reasoned that the best way to get cancer antigens into dendritic cells is to have those proteins produced within the dendritic cells themselves. To do this, they isolate and remove RNA from tumor cells and infuse it into dendritic cells. RNA thus "transfected" into a host cell uses that cell's machinery to make tumor proteins, which are then chopped up and displayed on the cell surface.
Many cancer immunotherapies may fail because they rely upon a single specific protein antigen that may or may not be found in that patient's tumor cells, Gilboa said in an interview. "It's difficult to find a protein fragment that works well for all patients, so the idea is to have a patient's own RNA make its cancer antigens."
To prove that the concept worked, the researchers refined the vaccine several times. The researchers reported that experimental progress in the April issue of the journal Nature Biotechnology. They first tested the vaccine using RNA that coded for a specific antigen known as CEA (carcinoembryonic antigen). CEA is often produced in breast, lung and colorectal cancer. They mixed this RNA sequence with dendritic cells, and the CEA was produced and displayed on the dendritic cells. Researchers noted a strong immune response when this concoction was exposed to the patient's cancer cells in a test tube. This type of vaccine is being tested in 18 patients whose tumors make CEA antigens.
In their current research, the researchers injected all the RNA from tumor cells into dendritic cells. The idea, said Nair, is that each patient's tumors produce a unique set of antigens that will induce potent immune responses to eradicate their cancer. Preliminary results from this research indicate that total RNA induced an even more potent immune response than the CEA antigen alone.