In cancer, the tumour microenvironment evolves over time, driven in part by exhaustion of T cells, with a reduced capacity to mount an effective immune response to the proliferating tumour. Modulation of checkpoint targets (e.g. PD-1, PD-L1, CTLA-4, OX-40, LAG-3, TIM-3 and others) on immune cells can help to reactivate and restore their normal effector function.
Aquila has established a murine in vitro CD4+ T cell culture system with an exhausted phenotype, to model T cell exhaustion observed in cancer patients, in which hyporesponsive T cells have a reduced capacity to target cancer cells. This immuno-oncology model is particularly relevant for understanding compound mechanism and efficacy, and is directly applicable for the development of immuno-oncology agents for cancer treatment.
The Aquila murine ‘Exhausted CD4+ T Cell Assay’ utilises a system whereby CD4+ T cell receptor transgenic T cells are stimulated with wild-type (WT) myelin basic protein (MBP) to produce fully responsive effector T cells, or MBP with an altered peptide ligand (APL-MBP), which acts as a superagonist to produce exhausted T cells. The ability of compound treatment to restore effector function to these cells can be tested by restimulating the cells with antigen in the presence of test substance or with our fully validated reference controls.
The exhausted CD4+ T cell assay can be used for high throughput screening (HTS) in 96-well plate format. Compound effects are determined by assessment of cytokine production by ELISA (e.g. IFN-ƴ) or additional readouts such as proliferation (e.g Ki-67, CFSE) using high throughput flow cytometry.
Contact us for more information on Aquila's Immuno-Oncology services.