The tumor microenvironment is comprised of blood vessels, infiltrating immune cells, cancer-associated fibroblasts (CAFs) and the extracellular matrix and provides a heterogeneous milieu with tumor-induced immunosuppressive properties. In combination with tissue specific structural features, it significantly contributes to tumor progression, immune evasion, and eventually treatment outcome. To mimic the tumor microenviroment more closely, we have established routine protocols for orthotopic tumor cell and fragment transplantation and continuously expand our portfolio of orthotopic CDX and PDX models. Together with our corresponding subcutaneous tumor xenograft models, we offer an extensive platform for efficacy testing as well as pharmacokinetic and biodistribution studies.
Available orthotopic models and readouts
Monitoring tumor growth and treatment responses in orthotopic PDX or CDX models often requires model-specific approaches. Apart from end-point readouts such as surrogate survival, tumor or organ size and weight, we can monitor tumor progression in vivo by bioluminescence imaging (BLI), ultrasound and flow cytometry for our hematological models. Orthotopic tumor models also metastasize much more frequently than their subcutaneously transplanted counterparts and thereby represent an excellent model system to study this crucial step during cancer progression. We have established protocols for the detection of metastatic lesions by either quantitative PCR or immunohistochemistry/histopathology.
Our available orthotopic/metastasis models are summarized in the table below:
| Entity | Orthotopic CDX | Luc-Tag | Metastasis |
|---|---|---|---|
| Breast cancer | 1 | yes | liver, lung |
| Pancreatic cancer | 1 | yes | liver, lung |
| Glioma | 2 | yes | no |
| ALL | 1 | ** | several organs |
| Ovarian cancer | 2 | no | peritoneum |
| Entity | Orthotopic PDX | Luc-Tag | Metastasis |
| Breast cancer | 7 | no | liver, lung |
| Pancreatic cancer | 3 | no | no |
| Glioma | 12 | no | no |
| ALL | 3 | no | several organs |
| AML | 3 | no | several organs |
| Neuroblastoma | 2 | no | no |
| Entity | Orthotopic syngeneic models | Luc-Tag | Metastasis |
| Breast cancer | 1 | no | liver, lung |
| Melanoma | 1 | no | lung* |
| Glioma | 1 | yes | no |
* after i.v. inoculation
** in progress