Access tumor models that can visualize FAP
Oncodesign Services has a deep experience in innovative model development to support preclinical studies of new targets and provide services that deliver high quality data in various fields such as oncology, inflammation or infectious disease.
Oncodesign Services has developed two mouse models that consider tumoral heterogeneity to better evaluate FAP biodistribution through in vivo imaging.
What is FAP?
FAP (Fibroblast Activation Protein) is overexpressed in a wide range of cancers as well as in tissues undergoing remodeling, such as scars and chronically inflamed tissues. Due to its low expression in normal tissues, FAP overexpression is linked to poor prognosis and can be used as a target.
Indeed, FAP plays a critical role in modulating the tumor microenvironment (TME) by degrading the extracellular matrix (ECM), which facilitates tumor growth, invasion and metastasis. Additionally, FAP is involved in the regulation of tumor angiogenesis and local immunosuppression.
Hence, FAP inhibitors are drug candidates widely investigated in oncology and more recently in inflammation. However, it requires the use of specific models to be as close as possible to the needs of drug discovery.
Mouse models with FAP expression
In reality, it is difficult to mimic in animals as FAP in patients is overexpressed in the TME. Therefore, ‘artificially’ overexpressing models were developed by transducing the cells.
Oncodesign Services has developed two mouse models with variable FAP expression, using Swiss Nude mice. This mouse strain is less radiosensitive allowing the evaluation of the radiotherapies over a longer time scale. The two preclinical models are pertinent as they present different levels of FAP expression and have a non/negligible FAP expressing parent model, hence mimicking inter- and intra-patient tumor heterogeneity. This allows more relevant evaluation of novel radiotherapies by minimizing the shift between preclinical and clinical results.
Examples of FAP models’ characteristics that match your needs
Using CDX models developed using Swiss Nude mice and two types of cell lines (HT-1080 & U87-MG), we transduced with FAP (respectively without FAP expression or with a base level expression) and monitored readouts over 10 weeks (tumor volume, body weight, %positive cells).
Image title: Graph of tumor volume and body weight evolution following engraftment in two FAP mouse models.
We observed that HT-1080-FAP model has a very rapid growth but is more heterogeneous whereas U87-MG-FAP has a slower tumor growth and more homogeneous.
Following flow cytometry analysis, FAP expression is confirmed in these two models (see graph below).
Image title: Ex vivo histogram quantification of FAP positive cells by FACS in two mouse models
To conclude, two preclinical models with variable FAP expression, taking account of patients tumoral heterogeneity were developed at Oncodesign Services.
Oncodesign Services is your partner in drug discovery providing innovative FAP mouse models that consider tumoral heterogeneity for the evaluation of your FAP inhibitors travers using in vivo imaging.
Do you need any support in your research program? Get in touch!