Restoring Normal T cell Effector Function in the TME
Exhaustion of T cells in the tumour microenvironment (TME) results in a reduced capacity to mount an effective immune response to the proliferating tumour. It is important to understand and evaluate the efficacy of compounds able to modulate checkpoint targets on immune cells and restore their normal effector function.
Aquila were the first CRO to develop a murine in vitro CD4+ T cell culture system with an exhausted phenotype, to model T cell exhaustion seen in cancer patients. The basis of our proprietary assay centres around our mouse TCR transgenic CD4+ T cells, which can be stimulated with WT-MBP to induce a fully responsive effector T cell, or with an altered ligand MBP (APL-MBP), which acts as a superagonist to generate exhausted T cells. These cells effectively mimic the exhausted state of T cells in the tumour microenvironment so are highly relevant to immuno-oncology research (Figure 1).
Figure 1. Exhausted T Cell Assay
Our moderate-throughput assay is ideal for evaluating the efficacy of compounds able to modulate checkpoint targets on immune cells. Your compounds can be tested against our validated reference controls. Several readouts are available to suit your requirements, including proliferation (e.g. Ki-67, CFSE) using flow cytometry, and cytokine analysis (e.g. IFN-γ) using ELISA or a multiplex approach (Figure 2).
Figure 2. Exhausted T cell Assay Readouts.
Building upon our reputation for innovation, we are currently validating an analagous human exhausted CD8+ T cell assay. This exciting new assay should be validated by Q4 2018.
Contact us today to learn more about our mouse and human exhausted T cell assays.