A synthetic gene circuit has been developed that can improve the efficacy of cancer immunotherapy.
Synthetic gene circuits that only trigger powerful, tumor-specific immune responses when they detect certain disease markers may help immunotherapies to fight cancer more effectively, according to a new study.
Researchers from the Massachusetts Institute of Technology (MIT) in Cambridge suggest that their artificial DNA-encoded circuits may help to overcome some of the problems that have dogged the translation of cancer immunotherapy from the laboratory to the clinic. They report their work in a paper that was recently published in the journal Cell.
Immunotherapy is a promising, albeit relatively new, type of treatment that enlists the patient's own immune system to fight the cancer.
There are several ways that it can do this. For instance, it can slow or stop the growth and spread of tumor cells, or it can help the immune system to destroy them more effectively.
Some immunotherapies have already been approved and are in clinical use. In 2011, for instance, the Food and Drug Administration (FDA) approved ipilimumab (Yervoy) for the treatment of advanced melanoma that cannot be removed through surgery. https://www.medicalnewstoday.com/articles/319804.php
The results of a new study suggest that killer T cells - which work to destroy cancer - could be made more effective if grown in a low-oxygen environment.
New research has suggested that an immunotherapy type that cultures patients' killer T cells in a laboratory before fine-tuning their cancer-destructive powers and returning them could be made more effective by growing the killer T cells in a low-oxygen culture.
Writing in the journal Cell Reports, researchers from the Weizmann Institute of Science in Israel suggest that their finding could increase the power of immunotherapy to fight solid tumors, which pose a particular challenge to killer T cells.
Killer T cells, which are also known as cytotoxic T lymphocytes (CTLs), are a specialized type of white blood cell called CD8+ T cells that are considered to be the "foot soldiers of the immune system."
CTLs directly kill damaged cells, cancer cells, and cells infected with viruses and other pathogens.
Senior author Guy Shakhar, who is a professor at the Weizmann Institute, explains that while killer T cells are the main agents of cancer immunotherapy, "they don't always manage to eliminate the malignancy."
However, he says that "by growing these T cells in an oxygen-poor environment, we can turn them into more effective killers."
Tumor cells can withstand low oxygen
At present, cancer immunotherapy that boosts patients' own killer T cells works best against certain leukemias and lymphomas. However, it is less effective at eliminating solid tumors, in which oxygen levels are very low.
Oxygen levels inside solid tumors, expressed as a percentage of gas dissolved in the fluid surrounding cells, range from 0.5 to 5 percent. This is lower than in most healthy organs and considerably lower than the 20 percent normally set for growing cells in the laboratory incubator.
Low oxygen does not appear to hamper tumor cells - for example, it does not stop them from taking in and metabolizing glucose, which is their main source of fuel.
But the low-oxygen environment of the tumor is not favorable to killer T cells. The researchers refer to several studies that offer evidence of this.