A small clinical trial shows that researchers can use gene editing to alter immune cells so that they can recognize a person's cancer-causing genes. The cells can be set free in the body to find and destroy their targets.
It is the first attempt to combine two hot areas in cancer research:gene editing to create personalized treatments and engineering immune cells called T cells so as to better target tumours. The approach was tested in a group of people with tumors.
Antoni Ribas, a cancer researcher and physician at the University of California, Los Angeles, is one of the study's authors. A patient's own T cells are being made into an army.
The results were presented at the Society for Immunotherapy of Cancer meeting.
Ribas and his colleagues started by looking for genes that aren't in the blood, but in the tumours. Each person in the trial had their picture taken. Ribas says that the cancer's genes are different. Although there are some similarities, they are not the majority.
A type of white blood cell called T cells patrol the body looking for stray cells. A lead author on the study says that T cells kill something if they see it is not normal. In patients with cancer, at some point the immune system lost the fight and the tumours grew.
After a series of analyses to confirm their findings, the researchers took blood samples from each participant and inserted the T-cell receptors into their T cells. The participants had to take medication to reduce the number of immune cells they produced.
Joseph Fraietta is a designer of T-cell cancer therapies at the University of Pennsylvania. The procedure can take more than a year.
The engineered T cells were given to each of the participants. The edited cells were found in higher concentrations in the blood than non-edited cells. Five of the participants had stable disease one month after treatment. The edited T cells are believed to have caused two people to experience side effects.
The researchers used small amounts of T cells to make sure the approach was safe. He says that they need to hit it stronger in the future.
The engineered cells will spend less time being cultured outside of the body and will be more active when they are infused. Fraietta believes that the technology will improve.
Solid tumours have posed a particular challenge in the treatment of engineered T cells. CAR T cells don't work against other types of cells, they only work against the tumours cells. There is no need to design new T-cellreceptors for each person with cancer because there is no need for such a thing.
Fraietta says that common surface proteins have not been found in solid tumors. Solid tumours give physical barriers to T cells, which must travel through the blood to the tumours and kill the cancer cells. Tumour cells can suppress the immune system by releasing chemical signals and using up the local supply of food and water.
Fraietta said that the environment around a tumours was like a sewer. As soon as they hit the site, T cells are rendered useless.
Mandl and her colleagues hope to be able to engineer T cells to be more active near the tumours with this initial proof-of-concept. Mandl says there are a number of ways to toughen up T cells, for example by removing the receptors that respond to immunosuppressive signals, or tweaking their metabolism so that they can more easily find an energy source in the tumours environment.
Thanks to recent technological advances, it could be possible to create elaborate designs for cell and gene therapies for cancer. He says it has become extremely efficient. Within the next 10 years, we will see very sophisticated means of engineering immune cells.
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