Nexus Bioquest is a CRO and preclinical specialist in immunology. Their work centres on building assays based on primary human immune cell subsets from both healthy and patient donors. These are validated cell assays, however most of them have been customised to fit target and biology of interest.
This presentation by Rhiannon Jenkinson highlights the importance of human in vitro models for the translatability of immunotherapy candidates. In inflammation and autoimmunity indications, these usually measure the immunosuppression of the candidate; for immuno oncology and infectious disease, they usually measure immune stimulation.
When building in vitro assays, the whole in vivo environment needs to be considered, which includes the anatomical location of cell-cell interactions. For example, cell interactions like the priming and activation of T cells and B cells need to be modelled as they occur within the secondary lymphoid organs. This is also the case for interactions within the tumour tissue or site of autoimmune function, which includes many cell subsets like epithelium cells, fibroblasts, specialised cells, and resident immune cells.
Jenkinson pointed to the mixed lymphocyte reaction (MLR) assay as a solid foundation for building complexity out from secondary lymphoid tissues. These assays can help in modelling cell-cell molecular interactions, but not the modulation of antigen presentation. Antigen-specific T cell biology and autologous dendritic cells can assist in modelling this kind of modulation. On top of this, there’s the tonsil reaggregate culture where secondary lymphoid tissue has been dis- and reaggregated to model the entire immune cell population.
The presentation highlights various molecules that can be tested, such as CTLA-4 blockers and PD-1 agonists, to modulate immune responses in autoimmunity and immuno-oncology. Jenkinson also explored dendritic cells as key players in immune responses, discussing methodologies for assessing their function and interaction with T cells. The role of neutrophils in inflammation and their potential as therapeutic targets were also highlighted, particularly in relation to NETosis and cytokine production.
The presentation concluded with a call for further exploration of immune resets and lasting tolerance in therapeutic strategies for both immuno-oncology and autoimmunity.
