Exhausted
T CELL ASSAY
Test your candidates in a more physiologically relevant in vitro system
Want to learn more about our Exhausted T Cell model? Contact one of our team now to see how we can help
T cell exhaustion is a phenotypic and functional state of a T cell. It is characterised by increased cell surface expression of checkpoint inhibitors and a reduced functional capacity.
Exhausted T cells exhibit reduced proliferation, a reduction in cytokine production and function. In the presence of repeated antigenic stimulation in the context of chronic infection or cancer, increasing numbers of T cells reach this exhausted state and are less able to perform their intended anti-viral or anti-tumor functions.
1. T cells are isolated from PBMCs and are stimulated in culture via CD3 and CD28.
2. Repeated stimulations produce T cells which exhibit sustained up-regulation of multiple checkpoint inhibitors PD-1, TIM-3, LAG-3, CTLA-4, BTLA and the transcription factor TOX
3. These cells are not anergic but are comparatively less proliferative, cytotoxic and able to produce IFNγ and IL-2 than resting T cells
4. In the presence of your therapeutic candidate, the exhausted T cells can be plugged into a functional assay of your choice; T cell cytotoxicity, T cell activation or mixed lymphocyte reactions
How are customer’s using the T cell exhaustion assay?
Although a key target for immune checkpoint blockade, exhausted T cell phenotypes are not well comprehended from a therapeutic point of view.
Immuno-oncology-based developers are looking to understand the pathways and molecular signatures governing the T cell exhaustion, in an effort to restore anti-tumour immunity.
Customers use our exhausted T cell exhaustion platforms to determine whether their therapeutic candidates can rescue or revitalize the functionality of the T cells in our human in vitro model, or when they are assessing their candidate’s ability to halt the progression of exhaustion, whereby their molecules are present during the in vitro exhaustion process.
In both approaches the T cells are phenotypically assessed by flow cytometry for expression of exhaustion markers, activation markers and any others deemed relevant to the mode of action of the customer’s molecules. Changes in cytokine production, proliferative response and functionality are all assessed to give the customer a clear understanding of how their molecule interacts and functions within a compromised tumour microenvironment model albeit an in vitro one.
Although every project is different, here at Antibody Analytics we have built a systematic approach to delivering complex customer studies while keeping the customer’s research needs at the heart of our assay set ups. Our T cell exhaustion methods have been standardized to allow our customers to insert their molecules into a method which is able to answer their developability and functional questions routinely and consistently. Alternatively, we can create a bespoke set up which is unique to you and the challenges you face.
If you are looking to test your molecule in a more predictable, standardized method, why not share some of your requirements in the form below and we can get a proposal out to you, or alternatively speak to our team and let us build a tailored approach to just for you.
CYTOKINE
RELEASE
T REG
SUPPRESSION
MIXED LYMPHOCYTE
REACTION (MLR)
T CELL MEDIATED
CYTOTOXICITY
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