Eureka Short: Novel Assay Tests CD8+ “Killer” T Cell Endpoints

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The immune system is dizzyingly complex, but basically breaks down into two major categories. There’s the innate immune system, which responds quickly to invaders via cells called neutrophils, natural killer cells and others. And then there’s the adaptive immune system, which is slower to act and includes B cells that produce antibodies and T cells that can differentiate into a myriad of pathogen-destroying derivative cells.

Just like invading microbes, some investigational drugs can stimulate or inhibit an immunological response by attaching to receptors on these immune cells. As a result, during the evaluation of a small molecule or biologic, the FDA requires that pharmaceutical and biotech companies employ a battery of functional assays to assess immunological endpoints. Such endpoints serve as a barometer for an activated or suppressed immune system.

Particular attention is paid to T cells. T cells are the shape-shifters of the immune system and break down into many subsets. But they can be categorized into two major ones: CD4+ T “Helper” Cells and CD8+ Cytotoxic “Killer” T Cells. Increasingly, the FDA has asked immunotoxicology programs to measure the activity of these later cells, which can directly attack virus- or bacterium-infected cells. The problem is that no functional assay exists for this T cell. And when companies ask for counsel, the FDA is often vague about requirements, in part because such cells are unique in function and hard to assess.

But Charles River’s Preclinical Services (PCS) facility in Reno, NV got a call from a sponsor, asking if they would be willing to try and create such an assay. Research scientists at the site agreed, and after tinkering, experimenting and overcoming many technical challenges, they succeeded in creating a functional assay that could evaluate Cytotoxic CD8+ T cell endpoints. It’s called the CD8+ “Ctx” assay. And while still in validation, it could represent a breakthrough in the field. More data will be generated over time as the sponsor uses the Ctx functional assay, but Charles River scientists think it could be used in the future as part of the standard battery of safety pharmacology tests that the FDA requires in the evaluation of a new drug’s impact on the immune system.

Thanks for listening to this Eureka Short. Its science in bite-sized form.

[The above text is a transcript of this podcast.]

As the Writer & Communications Specialist for Charles River, Dustin Grinnell writes and edits science articles as well as public relations and employee communications material. He has worked previously as a research scientist, science journalist and medical writer and has a Master’s degree in Physiology from The Pennsylvania State University.