New tool to assess the effect of immunotherapy
A team, led by Prof. Preet Chaudhary at the University of Southern California, has developed a new tool to test the effect of immunotherapy. The tool may also apply to other types of therapeutics and may be used to screen for environmental toxins.
Immunotherapy, any treatment that fights cancer by stimulating or suppressing the immune system, has become a research focus in recent years due to its potential therapeutic benefits. Several types of immunotherapy have been in development, including monoclonal antibodies, cytokines, immune checkpoint inhibitors, therapeutic cancer vaccines, T-cell therapy, and non-specific immunotherapies. Some immunotherapeutic agents have already been used to treat certain types of cancer in the clinic and have significantly improved patient outcomes.
According to Prof. Chaudhary, a big problem in the development of immunotherapy is the lack of ideal methods for testing the anti-cancer effects of immunotherapy. Currently, there are several assays for measurement of cytotoxicity induced by therapeutic agents. Of these, radioactive chromium release assay, which was developed in 1968, may be the most commonly used method to measure cytotoxicity by T cells and by NK cells. However, radioactive chromium release assay is expensive and time-consuming and involves the use of harmful radioactive substances. Thus, better alternative methods to measure the anti-cancer effects of immunotherapy are in urgent need.
Prof. Chaudhary's team tried to develop a novel assay based on luciferases, enzymes that produce bioluminescence. A wide variety of species use luciferase-mediated bioluminescence to startle predators or to attract prey or mates. These species include the firefly, the Jack-O-Lantern mushroom, many marine creatures, certain bacteria, etc. Due to their ability to emit light, luciferases have wide applications in biological research and clinic. For the current study, Prof. Chaudhary's team focused on luciferases found in marine animals. These marine luciferases have a smaller size, brighter luminescence and higher stability compared with some commonly used ones.
After a lot of work, Prof. Chaudhary's team developed a new cytotoxicity assay, called the Matador assay. The assay involves the expression of a luciferase in target cells. When these cells die, the luciferase will be released and produce a visible glow. The team used the assay to assess cytotoxicity induced by several types of immunotherapy, including antibodies, NK cells, chimeric antigen receptor (CAR) expressing T cells, and a bispecific T cell engager. They discovered that the Matador assay has great advantages over conventional assays. It is very sensitive, specific, rapid, and inexpensive.
The study suggests that the Matador assay, which is based on marine luciferases, may be a useful tool to evaluate the anti-cancer effects of immunotherapy. In addition, the Matador assay may have other applications, such as screening for environmental toxins.
Findings of the study have been summarized in a paper titled "Development and characterization of a novel luciferase based cytotoxicity assay," appearing online this week in the journal Scientific Reports.
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