IN VIVO TUMOR MODELS FOR CANCER IMMUNOTHERAPY

ONCOLOGY

To support drug discovery projects in oncology, we perform high-content analysis either in cellular models of human tumors in 2D or 3D, or directly in tumor tissues and blood samples. Combining a panel of validated assays for immediate performance and more than 10-year experience in assay development, we assist pharmaceutical companies and academic researchers in the discovery of new cancer drug targets, the identification of new anticancer compounds, and the quantitative analysis of novel cancer biomarkers.

IN VIVO TUMOR MODELS FOR CANCER IMMUNOTHERAPY

In recent years, a number of immune checkpoint inhibitors have been granted FDA approval. Although efficient, monoclonal antibodies targeting immune checkpoints have been found to produce objective and durable anti-tumor response in a limited number of cancer patients. To identify novel therapeutic strategies capable of enhancing the efficacy of immune checkpoint inhibitors, Fluofarma offers validated syngeneic mouse tumor model of anti-CTLA-4 and anti-PD-L1 immunotherapies.­­

PREDICTIVE IN VIVO MODELS OF ANTI-CTLA-4 & ANTI-PD-L1 CANCER IMMUNOTHERAPIES

  • Syngeneic tumor models: to closely recapitulate tumor-immune system interactions, tumor cells are inoculated into immunocompetent mice.
  • A well-characterized colorectal cancer model of immune checkpoint blockade, which responds to CTLA-4 inhibition but not to anti-PD-L1 immunotherapy
PD-L1 blockade enhances survival of GBM tumor-bearing mice. Combotherapy with compound X tends to improve this effect.

PD-L1 blockade enhances survival of GBM tumor-bearing mice. Combotherapy with compound X tends to improve this effect.

CTLA-4 blockade, but not PD-L1 inhibition, triggers a decrease of tumor growth in colorectal CT26 tumor-bearing mice model.

CTLA-4 blockade, but not PD-L1 inhibition, triggers a decrease of tumor growth in colorectal CT26 tumor-bearing mice model.

ASSESSMENT OF ANTI-TUMOR EFFICACY AND IMMUNE RESPONSE PROFILE

  • Preclinical efficacy study: Experimental groups (N=8-10) are monitored 3 times per week. Readouts include tumor size, survival and body weight.
  • Immune response assessment: satellite mice are added to each group for immune profiling at the tumor site or in peripheral compartments (spleen, lymph nodes) by flow cytometry or high-content imaging.
Flow cytometric immune cell profiling at the tumor site of vehicle-treated glioblastoma tumor-bearing mice.

Flow cytometric immune cell profiling at the tumor site of vehicle-treated glioblastoma tumor-bearing mice.

FLUOFARMA'S ADDED VALUE

  • Fast study initiation and weekly reports: syngeneic tumor models are set up and ready for treatment within 15 to 20 days after proposal validation. Preliminary reports are then are communicated every week.
  • Validated markers of immune response: CD4, CD8, CD25, FOXP3, CD11b, Gr1, CD11c, mPDCA1...
  • RTq-PCR analysis for immune-related genes: Il6, Ifng, Il17, Tnfa, Tgfb, Il10, Foxp3, Rorgt, Cd274 (PD-L1), Pdcd1 (PD1), …