- treatment against cancer that exploit the body's immune system to eliminate tumors began paying for some patients for whom all other treatments have failed. Now a small clinical study found support for a newcomer on the forehead of cancer immunotherapy. Injection of a vaccine designed to match specific mutations in their tumors, three patients with advanced melanoma have a strong immune response and, in two of their tumors shrunk or stabilized, at least temporarily. Although the study was primarily designed to test the safety, the results suggest that it is very promising to stop the growth of tumors.
"There is a lot of excitement about this approach," says oncologist and immunologist cancer Craig Slingluff of the University of Virginia in Charlottesville, who was not involved in the study.
vaccines for infectious diseases generally provide in the bits of body proteins and other materials from a virus or bacteria that trigger the immune system to defend against the invading pathogen . Cancer, the same idea is to vaccinate a patient with immune stimulating molecules, called antigens, found only on tumor cells so that the immune system of the person ends up attacking the tumor. But vaccines against cancer have a poor record of success. Indeed, most tumor antigens tested also appear in small quantities on healthy cells, and the immune system has mechanisms that make tolerate or ignore these familiar antigens.
Scientists have your eye on a more promising type of tumor antigen: those that result from mutations that riddle the DNA of a tumor through the chaos cancer causes genome. Some of these mutations do not appear in the genes that stimulate the growth of cancer, but encode novel proteins short peptides which can act as antigens on the surface of tumor cells. Because these so-called neoantigens are completely foreign to the body, they could, in theory, a vaccine against cancer.
Designing a vaccine against cancer neoantigen requires sequencing of a large number of tumor DNA, which was not possible or affordable until recently. But now that DNA sequencing costs have fallen and the increased speed, researchers at Washington University in St. Louis began exploring neoantigen cancer vaccines for melanoma, a tumor in which also creates light ultraviolet sunlight that creates carcinogenic mutations hundreds of additional mutations are likely to include many encoding neoantigens.
immunologist Human Beatriz Carreno, leader of the trial Gerald Linette and colleagues recently studied three patients with melanoma who underwent surgery to remove their tumor but had cancer cells that spread to their lymph nodes, that makes tumors likely to recur. Researchers have sequenced the exome or DNA encoding a protein, an original melanoma tumor of each patient and compared with the exome their other cells to identify tens of mutations encoding peptides newly created which could act as neoantigens. (All peptides produced by a cell appears on its surface.) They analyzed the structures of possible neoantigens and made laboratory tests to predict which are actually made by the cell and appears on its surface, then homed in on those most likely to trigger an immune response. For each melanoma patient chose seven specific neo-antigens on the tumor of this person.
After taking the blood of each patient, and harvesting thereof immune sentinel, dendritic cells, researchers were then mixed all neoantigens each patient with these white blood cells so that they see the peptides to other immune cells. The team used the neoantigen dendritic cells coated to make custom neoantigen vaccines that have been infused into the patients three times about 4 months.
Carreno and colleagues found that a key measure of vaccine response, the number of immune system T cells specific for neoantigens each patient has increased in the blood of patients and the increase the diversity of T cell-specific neoantigen These T cells could also kill the melanoma cells in culture expressing the same neoantigens, the team announced today online Science .
In one patient, metastatic tumors in the lungs of women has decreased, while regrew, but are now stable after 8 months; The remains of the tumor of the second person was also stable for 9 months. A third patient who had received an immunotherapy medication after surgery that put her cancer in remission remains cancer free. However, the trial was primarily designed to confirm the safety of the vaccine and immune response, not to test its effectiveness, and because patients received other treatments, it is impossible to say whether the vaccine helped: "I would be speculating if I said that the vaccine had no benefit to patients, "says Linette.
But the fact that the study found "a fairly high magnitude of the immune response," combined with recent reports that neoantigen different vaccine can fight against cancer in mice, suggests the idea is "promising," said Slingluff.
such a vaccine, which should be less toxic than chemotherapy, could be used to prevent cancer from recurring after surgery. It can also be combined with other immunotherapy drugs called checkpoint inhibitors that appear to work best for cancers such as lung and melanoma tumors in which many mutations. "the high anticipation is whether a one-two punch with inhibition control could function point, "said Roger Lo, a melanoma researcher at the University of California, Los Angeles.
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