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Secrets therapy chimeric receptor antigen CAR

November 8, 2018 13:42

Cancer is the second leading cause of death in the United States. According to the National Cancer Institute, this year will be diagnosed with some 1.7 million new cases, of which about 610 000 people umirut from the disease.

Fortunately, several recent cancer drugs show significant promise. Among them - the treatment of the chimeric antigen receptor (CAR), which the American Society of Clinical Oncology recently named the "Progress of the year 2018". Three researchers School of Engineering Sciences USA Viterbi - Assistant Professor Stacey Finley, professor Ping Wang and Associate Professor Nick Graham - published an article in "Biophysical Journal", which shed light on how this new treatment works, the information that one day may lead to better treatment of cancer with fewer side effects.

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"We are trying to understand the molecular mechanisms, - said Graham, assistant professor of chemical engineering and materials science. "Understanding how the CAR-cells, we could try to work out the best of them."

When the immune system is functioning properly, the immune cells move around the body and are looking for pathogens and kill them. However, cancer cells can disguise themselves, making it difficult to work with good cells such as T cells to kill them.

In therapy CAR T-cells human T-cells are removed, genetically engineered proteins, and then administered back into the patient. The resulting CAR T cells much better fight cancer cells. This is because these TAP modified cells are constructed CAR protein receptor, CAR, which can bind to cancer cells. When this occurs, the signal from the CAR reported T-cells began to destroy the cancer, highlighting chemicals perforin and granzyme.

TAP therapy

Earlier this year the US administration by the Food and Drug Administration approved the first therapy TAP-therapy for the treatment of some people with leukemia and late form of lymphoma. Early results have shown great promise. However, in earlier tests CAR-T-cell therapy hitherto proved much less effective against breast, lung, prostate and other solid tumors. In addition, some people receiving therapy treatment, there are significant side effects; some even died.

Three USC researchers hope that their performance significantly improve therapy TAP T cells, revealing a complex process, whereby the CAR activate cells that fight cancer. In particular, they studied a process called phosphorylation, which is a chemical reaction that occurs when the receptor CAR-bumps into a cancer cell and sends a signal to the T cell to attack the bad cells.

"I think the most interesting thing is that we did add in the understanding of any place in the CAR are phosphorylated how quickly this occurs and the amount of phosphorylation" - Finley said Gordon C. Marshall Chair of early career and an assistant professor of biomedical engineering, chemical engineering, materials science and life sciences.

In his studies, Finley, Wang and Graham know when and how phosphorylation occurs at six locations the CAR, that imperfect analogy can be described as "docking sites", according to Graham.

None CAR website should not be phosphorylated in front of others. Until now, scientists had only a general idea of ​​the process of phosphorylation, which hampered bioengineering TAP T-cells, which could successfully deal with difficult cancers of the breast, lung and other tumors.

Best fight against cancer

Finley, Wang and Graham hope to use their findings to develop more effective anti-CAR with fewer side effects. This may mean that phosphorylation is faster and more intense in some parts of the CAR, depending on the complexity of the target cancer cells. Alternatively, researchers could construct USC CARs phosphorylation less, thereby preventing excessive aggressiveness and fighting cancer cells and other cells of T- - a problem that has arisen as a result of early treatment of cancer TAP.

Already Finley built quantitative models, which have a great potential.

"Once we get these tools and quantitative models, we will be able to apply them to different projects CAR», - said Finley, whose research group has experience in mathematical models



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