Tumour Models Unit
Responsible person: Pavlína Janovská, Ph.D., M.Sc.
The tumour model unit is designed to enable the management, creation, and use of a wide range of mouse models of tumour diseases.
In addition to well-established models that are already available to customers and collaborators (see Services Offered), the unit will establish its own models, in particular genetically modified models (xenotransplantation of human cells – use of immunodeficient models vs. syngeneic immunocompetent mouse models), models resistant to standard therapeutic approaches, and so-called PDX (patient-derived xenograft) models.
Our goal is to create a portfolio of models that will enable us to answer key questions in preclinical development in the field of cancer therapy – describing the effect of a given treatment/genetic modification on disease development, its impact on the tumour microenvironment/immune system, or its effect on the development of resistance.
This unit can already actively participate as a strong partner or service provider in national and international research projects, as well as in consortia (such as EuroPDX). Models that are not yet available can be tailored to a specific project within the framework of long-term cooperation. Links to other units of the Masaryk University Preclinical Centre and the CEITEC core facilities will provide a unique opportunity for detailed analysis and interpretation of data.
Mouse models of cancer will be used to test the effectiveness of new experimental therapies or in projects aimed at understanding the biology of carcinogenesis. Tumour development will be monitored either directly in the unit using a multimodal imager or in collaboration with other PC units (in vivo imaging, analytical cytometry, histology, etc.).
What services/products will the unit provide?
Consultation
- ethical approval for in vivo experiments (mice)
- planning – design, (cohort size estimation, administration route, dose selection, controls selection etc.) readouts, timelines, coordination with follow-up analysis
- help with selection of suitable model, optimal endpoints
- transfer of animal models to the animal house
- education of students – handling of animals, dosing of animals, colony maintenance
Phenotyping
Testing of therapeutic doses, basic tolerability assessment
In vivo imaging of bioluminescence/fluorescence
Model establishment (based on published methodology, available mouse strains and cells – NOT de novo model development at this stage, with the exception of use of genetically modified cell lines)
- xenograft optimization for human cell lines to immunodeficient mice (primarily leukemic cell lines, solid tumour cells) – subcutaneous or orthotopic models
- syngeneic models
- in both cases – possibility to work with modified cell lines (CRISPR/Cas9 et., in vitro-induced resistant lines, Luc/fluorescently-tagged lines etc.) – provided by client/the Transgenesis unit of Preclinical centre
- engraftment efficacy testing
- in vivo resistance induction using the currently available in vivo models
Available models
- AML xenografts (in NSG, NSGS mice) – MOLM13, MV4-11, OCI-AML3, HL60
- CLL xenografts (in immunodeficient mice) – MEC1 etc.
- Eu-TCL1 syngeneic model – spontaneous or adoptive transfer variant (research collaboration only)
Prep of samples for subsequent analysis (complete or assistance, transfer to other units if needed) – e.g. proteomics, genomics, flow cytometry
(please discuss specific details in advance with Dr. Janovská; email: janovska@sci.muni.cz)
The unit will further develop and offer ex vivo models of tumour tissue, so-called tissue explants derived from clinical samples of solid tumours, e.g., ovarian or breast cancer. The analysis of clinical samples of solid tumours will also include their imaging using spatial multiplex immunofluorescence or spectral flow cytometry with the possibility of image analysis of cell populations (see the Immunology and Flow Cytometry Unit).
Services in the field of clinical samples of solid tumours:
Processing of tumour tissue into a single-cell suspension for subsequent immunophenotyping by spectral flow cytometry
Processing of tumour tissue for subsequent cultivation in the form of tissue explants
Multiplex spatial tissue imaging of the expression of up to 16 selected protein or glycan targets of validated fluorescent antibodies (from 2028)
(please discuss specific details in advance with Dr. Procházková; email: jirina.prochazkova@sci.muni.cz)