Recently, cancer researchers have devoted quite a sizeable chunk of their time and energy to making the human T lymphocytes, which play a central role in cell-mediated immunity, hone in on malignant tumours without damaging healthy tissues.
After many years of largely unfruitful efforts, Dr. Beatriz Carreno, a Human Immunologist at Washington University in St. Louis, USA had published a small, yet successful first trial in the journal Science.
Given that vaccines work through priming the T cells by exposing them to dead versions of a particular disease or to proteins distinctive to an individual virus or bacterium, a similar approach would be ideal for addressing cancerous tumours which normally offer much more time than most infectious diseases.
The problem with this technique – apart from its high price and currently low availability – is identifying appropriate features, or antigens, for the immune system to target.
Since the antigens cancerous cells express can also be found, albeit in smaller quantities, on the surface of healthy cells, targeting cancer-promoting DNA mutations is a much more viable solution. Some of these mutations do not appear in genes that drive cancer growth, but instead code for novel peptides (molecules that consist of 2 or more amino acids) which the T cells could target.
For this to work, however, each patient desiring to be treated with the vaccine would have to have her tumour sequenced, as the peptides to be targeted differ from person to person.
Carreno and her team chose to work on melanoma since the UV light that triggers the cancer also causes hundreds of other changes to the skin cells’ DNA, producing a wide range of antigens to target.
Having sequenced the exome, or protein-coding DNA, removed during surgery from three melanoma patients whose cancer had already metastasized into their lymph nodes, Carreno et. al. compared it to the exome of the patients’ healthy cells and selected seven antigens to target per person.
The antigens were then mixed with white blood cells drawn from the patients and re-injected back, with the process repeated three more times over the course of about four months. “This is about as personalised as vaccines can get,” said study co-author Dr. Elaine Mardis, also of Washington University.
Although the primary goal of the study was safety testing, the research team found their newly-created antigen-coated immune cells to elicit a significant response: “The tumour antigens we inserted into the vaccines provoked a broad response among the immune system’s killer T cells responsible for destroying tumours,” said lab leader Gerald Linette. The novel antigen-specific T cells also exhibited the ability to kill the cancerous cells in a cultured sample.
At the end of the trial, one of the patients was declared cancer-free, while the other two remained stable after 8-9 months. Since they also received regular treatment along with the immunotherapy, however, it is unclear as to how much (if at all) they have benefited from it: “I would be speculating if I said the vaccine had any benefit to the patients,” said Linette.
Combined with reports of a different antigen vaccine successfully fighting cancer in mice and the therapy’s low toxicity, the authors claim their new vaccine still shows a lot of promise in preventing cancer from recurring after surgery. A phase I trial has been approved by the FDA.