There are 3 main areas to take into consideration when developing your next preclinical program for CAR-T therapy. Lean how the selected tumor model, cell viability, and study duration play an important role in driving your preclinical success.
Have questions about how TD2 can assist with your regulatory needs? Reach out to our
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CT26 SC tumors: Gating strategy T cells and NK cells.
Gating involved identifying the total cell population, and then gate out the doublets, gate out the dead cells, move on to our first marker CD45 which gates out any non-immune cells. The bottom right cytogram shows the different NK cell populations. The far left middle cytogram depicts the two T cell population CD4+ and CD8+. Values are % of total CD45+ cells.
Screening tools for the evaluation of a drug’s ability to cross various biological membrane systems in a microplate format.
Figure 7. Example of Caco-2 Assay results. Assessment of the permeability of either Metoprolol (highly Permeable) or Quinidine (PgP substrate). A cell monolayer grown on a filtered-well is used to evaluate test compound movement between the insert (apical compartment -A) and the plate well (basal compartment -B). Passive transport through the layer is determine by A-B flux, whereas active transporter will introduce a B-A distribution of compounds between the two compartments.
In vitro drug metabolism studies, are a screening mechanism to characterize drug metabolites, elucidate their pathways, to help with further in vivo testing.
Figure 5. Observes relationship between inhibitor
(Ketoconazole) and the substrate (Midazolam).
Figure 6. Inhibition Profile for CYP3A4
Protein binding assays assesses the degree to which drugs attaches to proteins within the plasma/tissue. A drug’s efficacy may be affected by the degree to which it binds. TD2 has validated this assay using the Rapid Equilibrium Device and analysis done by LC-MS.
Figure 3. The process of protein binding assessment with rapid equilibrium dialysis.
Figure 4. Protein binding analysis by equilibrium dialysis of plasma
across mutiple different speacies (mouse, rat, dog, monkely, human)
following exposure to multiple compounds.
