PHENOMIN has developed expertise for oncology studies using mouse models for cancer progression and/or initiation. We are available to discuss projects, in close collaboration with users in order to customize any study to the scientific objectives applying the best adhesion to 3R rules.
PHENOMIN are regularly performing xenograft models for studying cancer progression. This is performed in syngeneic models, i.e. mouse tumors in isogenic mouse hosts, or human tumors xenografted into immunodeficient mouse models. Syngeneic models are superior for studying the immune response to tumors, whereas the immunodeficient hosts allow a greater array of tumors to be propagated. Syngeneic hosts may also be genetically modified to investigate other aspects of the tumor-stromal interactions. For non-invasive tumor tracking, we have developed a bank of bioluminescent tumor cells of human and murine origin (see listing below).
We currently perform cancer cell-line engraftment by subcutaneous, intravenous, or orthotopic injections. In particular, the development of ultrasound-guided injection offers orthotopic injection of tumor cells without surgery. We have validated cancer-cell injection in liver, kidney, spleen, and pancreas. Ultrasound guidance can also be used to locally inject therapeutic compounds or to realize biopsies.
PHENOMIN is at the cutting edge of mouse genetic models and can generate or access a wide panel of tumor initiation models. As part of the CanPathPro consortium, we are developing a predictive modelization platform for cancer initiation. CanPathPro Flyer (807.0 KB)
We also have an extensive repository of Cre- ERT2 lines for controlled ablation of genes over time with characterized tissue-specificity.
PHENOMIN is using CRISPR/Cas9 technology as well as homologous recombination techniques for custom model generation. Find out more at genetic engineering and mouse model validation services.
Readouts for oncology studies
We can apply numerous approaches to answer your scientific questions, including in vivo imaging, pathological investigation, and immunophenotyping.
In vivo imaging:
Tumor growth can be tracked by non-invasive imaging technologies. We have set up a preclinical imaging platform to monitor tumor progression, evaluate new therapeutic strategies by efficacy studies and approach fundamental research in collaboration with biologists and chemists. Our technological platform allows anatomic (X-ray, ultrasounds) as well as functional /molecular investigations (tomoscintigraphy a.k.a. SPECT, positron emission tomography a.k.a. PET, bioluminescence, fluorescence, photoacoustic).
For example, ultrasound imaging allows determination of a tumor’s precise location and volume (2D or 3D scans, for echogenic organs). The X-ray scanner is more appropriate for lungs or bones. We use bioluminescence to follow tumor growth and metastasis with high sensitivity. High sensitivity radioactive and fluorescence imaging techniques, can address a tumor biomarkers’ expression as well as radio- or fluoro-targeted compound screening. Photoacoustic imaging is used to visualize hemoglobin saturation and thus to elucidate the hypoxic dimension of tumors.
PHENOMIN can also provide ex vivo tumor characterization at the cellular or molecular level. Our anatomopathology facility can provide advances histological staining, standardized immunohistochemical (IHC) characterization for apoptosis (cleaved Caspase 3) and proliferation (Ki67), and custom IHC optimization and testing. We also offer detailed analysis of tumor pathology data for both human and murine tumors. At the nucleic-acid level, our ddPCR technology enables the detection of DNA or mRNA from very small amounts of tissue. This highly sensitive technique may be applied to rare genetic lesions and/or contrasting expression studies on small tumors or metastases.
In light of the complex tumor microenvironment, complementary experimental approaches have been used to assess the different cell types, their relative proportions, as well as their specificity. Flow cytometry is used to determine main lineages cartography of immune cells in different tissues. Mass cytometry is used to explore the functional state of a particular tumor infiltrating leucocyte lineage. Spectral cytometry is used to explore the impact of therapeutics on auto-fluorescent tumor cells and on their immune system escaping mechanisms by measuring checkpoint inhibitors’ ligand expression modulations. All together these data allow the determination of specific immune signatures characterizing cancer progression steps. The immunophenotyping is realized by using a combination of antibodies’ panels in flow mass and spectral cytometry. These panels (16 to 36 antibodies) allows the identification of lymphoid and myeloid populations which are present in a given organ or tissue. Specific panels for T, B, DC and NK cells are also validated in association with immune-modulator receptors, cytokines, chemokines and transcription factors.
Regarding pharmacokinetics and pharmacodynamics, we provide PK/PD analysison plasma samples from peripheral blood collection at different times (various routes of blood collection can be used). The impact of a therapeutic drug is assessed by analyzing cellular composition from several organss from a same animal. Tumor, blood, spleen, lymphatic ganglions are collected to perform high content immunophenotyping; the extensive characterization of tumor and tumor environment infiltrate requires a controlled cellular extraction which preserves surface markers.
Our oncology offer is summarized below. We can provide expert advice, define a targeting strategy, and ensure high scientific and technical output in accordance with your needs.
- Syngeneic models, Xenografts
- Tumor cells injection: sub-cutaneous, intravenous, orthotopic
- Echo-guided injection (orthotopic engraftments, drugs injection, biopsy)
- Polygenic and mosaïc models in targeted organs, in a somatic way, in adulthood (CRISPR/Cas9)
TUMOR CELL BANK
- Sub-cutaneous grafts
- Orthotopic grafts: murine lines and human lines
- Metastasis: bone, liver, lung.
- Anatomical in vivo imaging: tumor localization, volume measurement (Ultrasounds, X-ray)
- Functional/molecular in vivo imaging: following of tumor growth, evaluation of new therapeutic strategies (Ultrasounds, X-ray scanner, Bioluminescence, Fluorescence, Tomoscintigraphy, Positions emission tomography, Photoacoustics)
- Deciphering molecular mechanisms, signaling pathways (DNA, RNA, Protein analyses, ddPCR, Histological analyses, Immunohistological analyses and Apopotiosis anlyses.)
- Deciphering the Immune response in tumor environment and peripheral organs (Flow cytometry, Mass cytometry, Spectral cytometry, Specific panels, Spatial distribution of immunocytes and stromal cells within the tumor).
- Immune signature: cell states, differentiation state, functional and metabolic state, activated intracellular signaling pathways identification.