Therapeutic Applications of Regulatory T cells: modulating their role in vitro for cancer and autoimmunity treatment.
Regulatory T cells (Tregs) play a vital role in regulating the immune system by controlling the level of immune response. Tregs can inhibit unwanted immunity (e.g. in autoimmune diseases) but conversely can suppress desirable immunity in cancer. Small molecules and/or biologics have the potential to regulate Treg activity. Therefore, understanding not only the Treg function within the immune system but also how this is affected by potential drug candidates/compounds, plays a vital role in Immunology and Immuno-Oncology research.
The ability to test and modulate Treg suppression is a promising therapeutic area in both autoimmune and cancer treatments. In cancer, Tregs may be recruited and/or induced by tumours to maintain an immunosuppressive environment. Conversely, in autoimmunity, Treg suppression plays a dominant role in autoimmune pathology. Therefore, modulation of Treg activity is a promising therapeutic target for both cancer and autoimmunity treatment.
Aquila offers FoxP3+ Treg suppression assays to assess the ability of your compound to either boost or reduce Treg activity. We can assess your target compounds ability to alter the suppressive function of isolated ‘natural’ T regs (nTregs) and induced FoxP3+ Tregs (iTregs), more closely reflecting the FoxP3-induction believed to be driven by some tumours, and improving our capacity to model the tumour microenvironment (TME) (Figure 1).
Figure 1. Human Treg Suppression Assay.
Tregs can be co-cultured with autologous responder T cells or alternatively an MLR system with allogeneic APCs can be used. Readouts can be tailored to your requirements and can include the proliferative capacity of effector T cells with high-throughput flow cytometry and cytokine analysis (e.g. IFN-γ, IL-2, IL-10, TGF-ẞ) by ELISA or multiplex (Figures 2 & 3).
Figure 2. % Expression of Checkpoint markers on CD4+ CD25+ FoxP3+ T cells.
Figure 3. % Expression of Checkpoint Molecules on iTregs.
Aquila can help you understand the immunomodulatory effects of your drug candidates within the tumour microenvironment and/or in combination with other immune modulators. We offer a tailored program of work and data you can trust, giving you greater confidence in your lead compound selection. Aquila have extensive in vitro immunology, pre-clinical immuno-oncology and specialist multiplex histology experience. Our suite of immuno-oncology services and assays can be specifically customised to your project, efficiently progressing your route to clinic.
Get in touch to find out about how Aquila’s Treg Suppression Assays can further your Immunology and Immuno-Oncology drug discovery programmes.