Immunotherapeutic Discovery & Development
Validated with standard-of-care chemotherapeutics and small molecule inhibitors known to modulate immune responses, our predictive translational platform for immuno-oncology produces rich data to inform better decision making. Watch this video to learn more, and then see our step-wise approach for success below.
The promise of immunotherapies is reflected in its record number of clinical trials, yet these trials have produced the highest failure rates. Progress often comes to a grinding halt during syngeneic mouse in vivo studies. Why? The problem isn't with the therapeutic, but with the approach. Presuming knowledge of their lead compound, researchers often forge ahead without first fully characterizing their compound in more complex, disease-relevant environments. Given the complexity of the tumor microenvironment, it is imperative to create models that include all major immune cell types a compound may interact with.
What if there was a way to improve the chance that therapies translate more effectively across the discovery continuum? Investigating with a multicellular phenotypic assay enables us to take a different look at a compound's responses in a platform specifically designed to mimic the disease state. Optimized cellular assays provide critical information to validate the efficacy of a compound in simple and increasingly complex multicellular assays, delivering insights that serve as better predictors for the transition to in vivo studies.
Failed assays don't have to derail your development. Arming yourself with more information about your compound in a combination of assays improves predictability of its performance in in vivo, syngeneic models, humanized models, and ultimately, the clinic. Charles River's translational platform for immuno-oncology supports the collection of rich data to inform better decision-making, moving you effectively from target discovery and validation through to humanized mouse models and on to the clinic.
Start with in vitro assays.
Primary Cell and Co-Culture T Cell Assays
Optimized T cell-based assays provide critical information to validate the efficacy of a compound in simple and increasingly complex multicellular assays, delivering insights that serve as better predictors for the transition to in vivo studies. Real-time immunoreactivity provides crucial characterization of your compound’s immune cell activation, mechanism of action T cell clustering, and cancer cell killing. Monitor functional recognition of T cell proliferation and apoptosis in real-time.
Translate to in vivo syngeneic mouse models.
In Vivo Efficacy
Syngeneic mouse models provide an effective approach for studying how cancer therapies perform in the presence of a functional immune system. Our portfolio of syngeneic models has been well-characterized in their responses to known immune checkpoint inhibitors (e.g., anti-PDL-1, anti-PD-1, anti-CTLA-4). The majority of our models have also undergone whole exome sequencing to enhance your model selection, giving you the ability to choose based on mutation status in addition to sensitivity to immune checkpoint inhibitors.
Translate to ex vivo analysis.
2D and 3D high content analysis of cell lines derived from our portfolio of patient-derived xenograft (PDX) tumor models allows you to use the same models for in vitro, ex vivo and in vivo analysis. Our PDX models retain characteristics such as heterogenous histology, clinical biomolecular signature, malignant phenotypes and genotypes, tumor architecture, and tumor vasculature. Visit our Cancer Model Database to determine which PDX model is best for your studies. Assessment of potency and selectivity, identification of mode of action and analysis of multidrug resistance can be observed in both 2D or our patented 3D assays using our proprietary PDX explants.
Verify in an immunologically competent host.
Humanized mice harbor known human immune checkpoint inhibitors to provide a more clinically relevant host. We offer two study types using humanized mouse models (NOG, NSG, and the new NCG) engrafted with CD34+ or peripheral blood mononuclear cells (PBMC). CD34+ models contain hematopoietic stem cells derived from the umbilical cord; multiple donors in each cohort support long-term studies without graft versus host disease (GvHD). PBMC models involve a single cohort of animals engrafted with a single donor for short-term studies due to GvHD.
- Translational Platform for Immuno-Oncology Discovery (Publication)
- Predictive, Translational: Optimizing Immuno-Oncology Discovery (Webinar)
- Review the data presented at AACR2018 (Poster)