Drug efficacy in vivo studies 

At InnoSer, we frequently carry out in vivo efficacy studies in a range of preclinical models (patient-derived xenografts, syngeneic models, cell-line derived xenografts) complemented with readouts such immune cell profiling and histopathology. Click on the links below to view some examples of validated models such as the MC38 colorectal carcinoma model or peritoneal carcinomatosis model.

To assess disease progression and efficacy, we frequently make use of non-invasive in vivo imaging methods such as bioluminescence imaging (click here to view example data) and/or ultrasound (Figure 1).  

FIGURE 1. Implantation of Renca cells orthotopically in the kidney allows the study of renal cell carcinoma treatments, highly relevant in the context of immunotherapies. (A) Following initial cell culturing, murineRENCA cells at different cell densities (10, 000, 50,000, and 100,000 cells)were orthotopically injected. Compared to healthy kidneys (B), kidneys of mice injected with Renca cells (C) lead to an increase in total kidney volume and development of lesions, which can be longitudinally imaged and quantified. ​

To gain additional insight in the TME, multiplex fluorescence staining (> 20 markers) & imaging can give spatial information on the interaction between tumor cells, stromal cells and infiltrating immune cell populations. In addition, flow cytometry analysis allows immune cell profiling of both isolated tumor & TME cell populations as well as blood or spleen immune cell profiling.   

Drug efficacy in vitro studies 

Your in vivo immuno-oncology research can be simultaneously complemented with a wide range of in vitro culture assays (immune cell profiling, macrophage polarization, cytokine release analysis, T-cell activation/proliferation, B-cell activation/proliferation, dendritic cell maturation, immune risk assessment etc.), performed using primary cells (PBMC-derived) or human cell lines. The assays can be performed in conventional 2D or 3D (co-)cultures, or in organ-on-chip platforms.  

An example application of in vitro macrophage polarization assay and immunotherapy-induced macrophage toxicity is shown in Figure 2. Trametinib (inhibitor of MEK1 and MEK2) significantly increases the M1 profile of macrophages but also affects the viability of macrophages compared to untreated cells, while the P13K inhibitor (LY294002) shows opposite effects of Trametinib (Figure 2).  

FIGURE 2. Macrophage polarisation can be studied in vitro to evaluate the mechanism of action (MoA) of novel immunotherapies. Effect of PI3K inhibition (LY294002) and MEK1/2 inhibition (Trametinib) on polarisation of M1 macrophages: HLA-DR expression shown as (A) percentage (%) and (B) mean fluorescence intensity (MFI). Effect of PI3K inhibition (LY294002) and MEK1/2 inhibition (Trametinib) on viability of macrophages showing Trametinib-induced immunotoxicity of M1 cells (C).  

Effects of chemotherapy on cognition– chemo brain evaluation 

Besides evaluating the efficacy of novel anti-cancer treatments, experts at InnoSer have experience with evaluating extra-systemic effects, focusing namely on brain health and cognition. Patients undergoing chemotherapy treatments often experience a decline in cognitive function and memory – commonly referred to as the chemo brain.  

Similarly to cancer patients, administration of chemotherapy in mice is associated with decline in cognitive performance. Together with researchers from The Netherlands Cancer Institute (NKI), we have previously shown that administration of several cytotoxic chemotherapies impacts a wide range of cognitive domains using highly standardized behavioral tests (Seigers et al., 2015).