Customized cancer vaccines designed for a patient’s individual tumor have displayed success in a small study, helping the immune system in combating cancer in a better way. But the real challenge is going to be, how to make the process affordable.
T cells are one of the vital elements of the immune system. Their potential to pinpoint abnormal cells and target them for destruction is a critical part of this. Certainly this potential is scanty, however, and discovering ways to improve T cell discrimination between cancers and healthy cells has become a major research project. After decades of frustration, Dr. Beatriz Carreno of Washington University, St. Louis, has reported in Science a successful yet extremely small, trial.
Vaccines, like those utilized against polio or measles, prime T cells by baring them to dead versions of the disease or to proteins unique to the virus or bacterium. Once the cells have been conditioned to identify the invader, they can react much more swiftly to a real attack. Given that cancers offer much more time than almost all infectious diseases, a nearly identical approach would be perfect were it not for the challenge of finding the right features for the T cells to target.
Despite the fact that cancer cells express proteins that could possibly be used as antigens, or targets, for T cells, these same antigens as well show up on the surface of healthy cells, although in smaller quantities. A second path is to concentrate on mutations in the DNA of cancer cells. Cancer tends to scramble the genome, and the mutations produced will prompt the creation of peptides that will usually occur nowhere else in the body. While these peptides let T cells hone in on cancers while leaving healthy cells alone, they have an issue of their own – every person’s peptides will be dissimilar. As a result, it is impossible to make a single vaccine against a type of cancer. Rather, cells must be accumulated from each individual’s cancer and then sequenced.
Carreno opted to work on melanoma since the ultraviolet light that activated the cancer also precipitates other damage to skin cells’ DNA, generating a wide array of antigens to target. She sequenced DNA pulled out in the course of surgery from three melanoma patients and compared each one with equivalent genes removed from healthy cells. Potential antigens were examined for each patient and seven were picked per person. The selected antigens were mixed with white blood cells extracted from the patient and then re-injected, with the process replicated 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 main motive of the study was to test for safety. Nonetheless, 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 generated T cells destroyed cultured samples of the tumors. One of the patients has been declared free of cancer. Rest of the two had inoperable tumors left over after the primaries were removed. In both cases, the cancers stopped growing 8-9 months after the process. Nonetheless, in neither case is it feasible to conclusively credit the vaccine since other treatments were also used. Nonetheless, the combo of low toxicity and T cell production has raised hopes. FDA has already approved phase I trial on six patients.