Cancer vaccines tailored-made to a patient’s individual tumor have shown success in a small study, assisting the immune system in combating cancer more effectively. However, making the process affordable is likely to prove an even bigger challenge.
T cells are one of the key elements of the immune system. Their capacity to identify abnormal cells and target them for destruction is a vital part of this. Inevitably this capacity is limited, however, and finding ways to improve T cell discrimination between cancers and healthy cells has become a major research project.
After years of frustration, Dr. Beatriz Carreno of Washington University, St. Louis, has announced in Science a successful, albeit very small, trial.
Vaccines, such as those used against polio or measles, prime T cells by exposing them to dead versions of the disease or to proteins distinctive to the virus or bacterium. Once the cells have been trained to recognize the invader, they can react far more quickly to a real attack. Given that cancers offer far more time than most infectious diseases, a similar approach would be ideal were it not for the challenge of finding appropriate features for the T cells to target.
Although cancer cells express proteins that could potentially be used as antigens, or targets, for T cells, these same antigens also appear on the surface of healthy cells, albeit in smaller quantities.
An alternative path is to focus on mutations in the DNA of cancer cells. Cancer tends to scramble the genome, and the mutations produced will cause the production of peptides that will often occur nowhere else in the body. While these peptides allow T cells to hone in on cancers while leaving healthy cells alone, they have a problem of their own – every person's peptides will be different. Consequently, it is not possible to produce a single vaccine against a type of cancer. Instead, cells must be collected from each individual's cancer and then sequenced.
Carreno chose to work on melanoma since the ultraviolet light that triggers the cancer also causes other damage to skin cells' DNA, producing a wide selection of antigens to target. She sequenced DNA removed during surgery from three melanoma patients and compared each with equivalent genes taken from healthy cells.
Potential antigens were analyzed for each patient and seven were selected per person. The chosen antigens were mixed with white blood cells drawn from the patient and then re-injected, with the process repeated three more times over several months. “This is about as personalized as vaccines can get,” said co-author Dr. Elaine Mardis of Washington University.
The primary purpose of the study was to test for safety. However, lab leader Dr. Gerald Linette said, “The tumor antigens we inserted into the vaccines provoked a broad response among the immune system’s killer T cells responsible for destroying tumors.” The newly produced T cells killed cultured samples of the tumors.
One of the patients has been declared cancer-free. The other two had inoperable tumors left over after the primaries were removed. In both cases, the cancers were not growing 8-9 months after the process. However, in neither case is it possible to definitively credit the vaccine since other treatments were also used. Nevertheless, the combination of low toxicity and T cell production has raised hopes. A phase I trial on six patients has been approved by the FDA.