Immuno-oncology has emerged as an important approach for the treatment of cancer by activating or augmenting the body’s natural response to fight the disease. Immuno-oncology efficacy studies require the use of tumor models with an intact immune system. For that, EPO offers a broad collection of humanized and syngeneic models.
Critical differences in certain components of the immune systems, particularly myeloid cells, can lead to species-specific tumor-host interactions. These differences can be overcome by conducting preclinical studies in fully humanized models. We offer in-house humanization with various immune cell populations including their preparation, isolation and enrichment. Immune cells can be isolated from a set of curated blood donors and HLA matched with the respective PDX tumor models.
The following cell types can be used for humanization:
- CD34+ hematopoietic stem cells (HSC)
- Peripheral blood mononuclear cells (PBMCs)
- Purified T cells (also subpopulations possible)
- Purified NK cells
- Purified, in vitro expanded NK cells
Depending on the specific study requirements, a broad variety of severely immunodeficient strains (e.g. NOD/SCID, NOG, NOG-EXL) can be used for humanization.
In our humanized models, we have already tested the following immune- and cell therapeutics:
- CAR-T cells
- TCR-T cells
- CAR- NK cells
- Bispecific antibodies
- Trispecific antibodies
- Bi-specific T-cell engagers (BiTEs)
- Immune checkpoint inhibitors
- Small molecules
We support our clients in understanding the mechanism-of-action of their compounds by detecting immune or tumor cells with various methods such as flow cytometry, immunohistochemistry or in vivo imaging. Furthermore, in vivo studies can be accompanied by in vitro cell assays using the Incucyte® Live-Cell Analysis System.
For syngeneic tumor models, murine or rat tumor cell lines are inoculated into their respective syngeneic background. This provides a robust and cost effective approach for studying how cancer therapies perform in the presence of a functional immune system. We have a broad collection of syngeneic tumor models available and our models are well characterized and benchmarked against the most common immune-checkpoint inhibitors as well as combination therapies including radiotherapy. Tumors in these models can be immunophenotyped by either flow cytometry or immunohistochemistry upon study conclusion. For both methods we have an established set of markers available.
Flow cytometry services
Flow cytometry is a powerful method for the expression analysis of cell surface and intracellular molecules and the characterization of different cell types in a heterogeneous cell population by using fluorescence labeled antibodies. EPO offers multiplex flow cytometry assays for various applications including the immunophenotyping of our humanized models, the analysis of immune infiltrates in tumor tissues and the evaluation of immune-modulating drug effects. For that purpose, our scientists have developed and validated flow cytometry panels for several relevant immune cells including T cells, myeloid-derived suppressor cells, macrophages, and natural killer cells. In addition, we routinely develop customized panels for the identification of specific immune cells critical to a particular research program.