in vivo orthotopic tumor model of glioblastoma

The search for new anti-cancer agents therapies and treatment modalities is continuously requiring the development and availability of valuable in vivo tumor models, including, among others, orthotopic models. These, based on an orthotopic tumor implantation as opposed to heterotopic inoculation, permit accurate expression of the biological tumor nature in terms of growth rate, morphology and metastasis, thereby mimicking the disease progress for an accurate assessment of response to anti-cancer therapies.

We are offering the following orthotopic tumor-bearing syngeneic mouse models to perform in vivo efficacy evaluation, which can be built by ex vivo capabilities for biomarkers analysis and immune response characterization.

GBM model characteristics

 

Apart from the advantage of the tumor cells (stably expressing the 2nd generation firefly luciferase) which are intracranially implanted by stereotactic surgery, our syngeneic GBM model mimics the major human disease features including immune cell activation and infiltration, and astrogliosis, among other characteristics, and therefore allows for testing drug candidates for their ability to enhance or restore the anti-tumor immune response, in a functionally immunocompetent system.

GL261_IHC_microglia

GL261 glioma tumor-bearing model is characterized by tumor-infiltrating microglial. Immunohistochemistry processing associated with H&E staining highlights the presence of tumor-surrounding (A&B) and tumor-infiltrating (B&C) Iba1-positive microglial cells.

GBM model for chemotherapy and immunotherapy assessment

 

Explicyte set up and validated the syngeneic GBM mouse model to assess novel combination regimens with chemotherapy or immunotherapy. Robust treatment protocols combined with validated gold standard chemotherapeutics and immune checkpoint inhibitors have been optimized and allowed to characterize and validate GL261 glioma as responsive to Temozolomide (TMZ) and to anti-CTLA-4 treatment.

In Vivo Efficacy And Profiling Of Anti-Tumor Response

 

  • Standard efficacy package: Tumor growth and progression are monitored and quantitatively measured by BLI along the study. Tumor growth, body weight and survival are assessed weekly in experimental groups of standardly 10 mice, to test a drug candidate alone and in combination with a chemo- or immunotherapeutic reference.

Glioblastoma GL261 GBM

Delayed tumor development in anti-CTLA-4 and TMZ-treated GL261-Luc2 tumor-bearing mice.  Mice were implanted with GL261-Luc2 glioblastoma tumor cells, and exposed either to TMZ or anti-CTLA-4 antibody. Tumor growth was followed overtime and determined by in vivo bioluminescence imaging.

 

  • As for our satellite immune response profiling studies for MOA deconvolution, satellite mice (N=4) can be added to each group to study the impact of a treatment on immune response modulation at the tumor level and/or peripheral compartments. Immune function can be studied using appropriate methodologies and platforms, e.g. flow cytometry, RT-qPCR, immunohistology-based imaging.

Immune profiling MDSC GBM

Immune cell profiling and flow cytometric detection of MDSC (CD11b+/Gr1High) and FoxP3+ immune cells within intracerebral GL261-Luc2 glioblastoma. Results show the presence of immune suppressive cells with a majority of FoxP3+ cells being CD4 negative.

Our added value

 

  • Weekly progress reports: the first report is sent within 10 days after study initation. Weekly reports enable to adjust the study design according to the results.
  • Longitudinal mice bleeding: blood samples can be collected every week, allowing the monitoring of peripheral markers over time in responding and non-responding animals.
  • A strong expertise in syngeneic tumor models of immune checkpoint inhibition: Explicyte offers a range of in vivo tumor models including orthotopic and subcutaneous models for anti-CTLA-4 and/or anti-PD-1/PD-L1 therapy.

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Explicyte immuno-oncology offers to test novel cancer immunotherapies in a syngeneic glioma tumor-bearing model suitable tool for assessing both in vivo efficacy and MOA for brain cancer strategies. IThis model is characterized for anti-CTLA-4 antibody and Temozolomide (TMZ) responses.