Aquila’s MBP-Tracker screening platform incorporates sophisticated in vitro and ex vivo analysis, enablingw detailed interrogation of the fate of antigen-reactive, pathogenic T cells, from simple expression of cell surface molecules, to immune-purification, allowing downstream transcriptome analysis. In vitro assays can be used to screen larger numbers of compounds before progressing to in vivo T cell priming studies or MBP-Tracker EAE, which allows specific assessment of traceable, antigen-reactive cells ex vivo.
Stage 1. In Vitro
In vitro MBP-reactive T cell assays offer a time efficient screen to determine on-target compound effects following antigen specific-TCR stimulation. The use of MBP-reactive splenocytes in vitro has the benefit of physiologically relevant TCR stimulation by MBP peptide antigen, to more accurately model in vivo activation of pathogenic T cells and the ability of compound to affect phenotype/effector function.
Compound effects can be assessed prophylactically or therapeutically upon re-stimulation of activated splenocytes:
Stage 2. In Vivo Priming
In vivo priming of MBP-Tracker cells is used to determine on-target compound effects in short, cost-effective in vivo studies. Ex vivo analysis of primed MBP-Tracker cells in response to compound can be determined by:
Stage 3. In Vivo MBP-Tracker EAE
Our unique EAE model allows us to obtain clinical efficacy and mode of action data from individuals treated prophylactically or therapeutically with compounds. Pathogenic MBP-Tracker cells can be isolated from both peripheral lymphoid organs and CNS to elucidate compound mode of action by: