Scientists create an effective protein against cancer cells

Tomorrow – Scientists have created a new protein that has no toxic effect and has been shown to be effective in fighting cancer cells in animals.

Scientists from the Institute of Protein Design at the University of Washington have created a new protein mimicking the main immune-regulating protein, interleukin-2. This protein is a potent cancer antagonist and effective treatment for autoimmune diseases, but its toxic side effects limit its clinical benefits.

In a study published Jan. 10 in the journal Nature, researchers reported that they could use computer programs to design an effective protein in animals and able to stimulate cancer-fighting T-cells. interleukin. 2 naturally, but this new protein without undesirable side effects.

This breakthrough opens up new approaches for designing protein-based treatments for cancer, autoimmune diseases and other disorders, the researchers said. According to a report from "Science Daily".

Simulation
The new protein called New 2/15 because, in addition to simulating the effect of interleukin protein, it could mimic the effect of another protein called interleukin-15, which is studied as a potential treatment for cancer.

"Thirty years of attempts have been made to alter the interleukin-2 protein, making it safer and more effective in terms of use," said researcher Daniel Adriano Silva, a biochemist at the University of California. Institute of Protein Design at the University of Washington. But since naturally occurring proteins tend to be very stable jealousy, it is very difficult to do so.

"The new 2/15 protein is very small and stable, and as we have designed it from scratch, we understand all of its components and we can continue to improve it, making it more stable and stable. active. "

"The new 2/15 protein has good therapeutic properties, such as interleukin-2 protein or higher, because it is computationally calculated to be less toxic," said Ote Olegi, a physician in internal medicine and biochemist at the University of Ottawa. Institute of Protein Design, University of Washington. A lot. "

Interleukin-2 protein was used as a final treatment for cancer patients who had no other treatment option. This protein can achieve a cure rate of up to 7% for some patients with advanced melanoma or kidney cancer.

Limited use
However, this protein is used in a limited way because it can be administered only to healthy patients in intensive care units of specialized medical centers.

Interleukin-2 acts on two types of immune cells by binding to receptors on the surface of cells. The effect of this protein depends on the behavior of the cell, in particular the number and nature of the interactions of these receptors. The natural interleukin-2 can activate cells with beta and gamma receptors responsible for anti-tumor activity, which exactly matches the wishes of the patient.

However, normal interleukin-2 is preferentially badociated with another type of immune cell having alpha receptors, as well as beta and gamma receptors.

It is worth mentioning that these cells have harmful side effects, such as a serious toxicity and reduce the activity of the immune system. Unfortunately, all interleukin-2 protein-based therapies have to date resulted in preferential activation of these cells outside the target.

Enhanced properties
In contrast, the new protein does not bind favorably to the harmful cells: this new molecule can activate the tumor cells without activating the cells responsible for the toxicity and weaken the immunity.

Research has shown that designing proteins from scratch can lead to the production of biomolecules with improved therapeutic properties and the reduction of side effects of any biological molecule, said David Baker, professor of biochemistry at the Faculty of Medicine. Washington and investigator at Howard Hughes Medical Institute. Its shape is known or predictable.

For the design of proteins, the researchers used a computer program developed by Baker's lab, Rosetta, to design a protein whose surfaces could bind and activate beta-2 beta and gamma receptors, and not the receptors in the cell. Interleukin-2 alpha, which are part of the malignant cells.

The researchers first designed the integrated proteins that would serve as vectors to install with the receivers in the right place. They then improved the amino acid sequence of the best tankers, which allowed the creation of the new protein.

In laboratory and animal models, this protein was badociated with interleukin-2 beta and gamma receptors, activation of immune cells to fight cancer and slower tumor growth. As the synthetic protein has no binding site for the alpha receptor, the effective doses of the modified version of the new protein 2/15 do not cause toxic side effects.