06 April 2015

Dendritic cells against melanoma

Cancer vaccine created from mutated tumor proteins

Asya Gorina, VestiA team of researchers led by specialists from the Washington University School of Medicine in St. Louis has developed a prototype of a cancer vaccine from mutated tumor proteins.

This work has become a small breakthrough in personalized medicine, on which most hopes are placed in the fight against cancer.

Clinical trials of the vaccine were conducted as follows. The researchers took a tumor sample from a patient, isolated mutated proteins from it, and then manufactured a drug. As reported in an article published in the journal Science (A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells), three volunteers who received the vaccine demonstrated a powerful immune response.

The problem is that researchers do not yet know whether the received immune response is enough for the tumor to stop growing. Until now, medicine has not established norms for the manifestation of an immune reaction that would lead to remission. Therefore, it will be possible to verify the success of the vaccine trial only in practice.

Cancer is a genetic disease, the development of which is provoked by special mutations. The development of oncological diseases is associated with uncontrolled cell growth in various tissues of the body, and this process is caused by pathogenic mutations in genes.

However, mutated proteins produced by cancer cells can also serve a good service: their presence in the body is a kind of alarm signal for the immune system. The immune system perceives this signal as an invasion of foreign cells or bodies and puts all its forces into battle with the "invader".

Unfortunately, such a process does not always start naturally. Some tumors suppress immunity, and mutated tumor proteins cannot be expressed in sufficient quantities to rally immune cells to fight.

"Researchers have long dreamed of using mutated tumor proteins to their advantage – to create an anti-cancer vaccine. However, before there were not enough technological solutions to implement this idea," says lead author of the study immunologist Beatriz Carreno from Washington University in St. Louis.


Dr. Carreno and her colleagues are working on the production of an anti-cancer vaccine
(photo: Tom Kitchen, Washington University School of Medicine in St. Louis).

The key to the solution was the technology of genome sequencing and understanding the functionality of the immune system. Previously, researchers have demonstrated that a vaccine made from mutated tumor proteins provokes a strong immune response in mice, and now Carreno and her colleagues show that the same is true for humans.

Scientists sequenced the tumor genome in samples taken from three patients with melanoma (skin cancer), and then cataloged mutant proteins in each sample. The biochemists then selected seven protein fragments for each patient and used them to make the vaccine.

White blood cells were also taken from each volunteer, which were then cultured in the laboratory to create special immune cells – the so-called dendritic cells. These cells were later exposed to protein fragments, after which the entire mixture was injected into patients.

Dendritic cells bound to fragments of the mutated protein and thus immune cells received a direct tip to cancer cells. As a result, a strong immune reaction was observed two weeks after vaccination, according to a press release (Personalized melanoma vaccines marshal powerful immune response).

In the near future, Carreno and her team will try to explore the possibility of manufacturing and using an anti-cancer vaccine for other types of cancer. Unfortunately, all of them are characterized by their mutations and proteins, and therefore there can be no universal method. However, the introduction of a personalized vaccine is today one of the most promising ways to save a person from cancer.

Portal "Eternal youth" http://vechnayamolodost.ru06.04.2015

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