Tumour mutations harnessed to build cancer vaccine

Heidi Ledford in Nature:

Cancer is a genetic disease, driven by mutations that lift the brakes on cell proliferation. But the mutated proteins produced by cancerous cells can serve as a siren call to immune cells, signalling the presence of a cell that has become, in a sense, ‘foreign’. Unfortunately, many of these calls are never heard. Some tumours suppress nearby immune responses, and mutated tumour proteins may not be expressed at high enough levels to rally immune cells. Researchers have long dreamed of using those mutated proteins to generate a vaccine, says immunologist Beatriz Carreno of Washington University in St. Louis, Missouri, but lacked the technological wherewithal to do so.

The advent of cancer-genome sequencing and an improved understanding of the immune system have converged to make that approach possible. Last year, two groups^{2, 3} showed that such vaccines can work in mice. Carreno and her colleagues have now taken the approach into humans. The researchers sequenced the tumour genomes in samples taken from three people with melanoma and catalogued the mutated proteins in each sample. They then chose seven protein fragments per patient for use in the vaccine. White blood cells were taken from each patient and cultured in the laboratory to generate immune cells called dendritic cells. These cells were then exposed to the protein fragments, allowed to mature in the laboratory and then infused into the patients. By then, the dendritic cells had taken up the protein fragments, and were able to present them to immune cells in the body. The result: immune cells trained to target the mutated proteins produced by the tumour¹. Such immune cells were evident in the patients' blood two weeks after vaccination.

More here.