In vivo orthotopic breast tumor model

Orthotopic tumor inoculation allows organotypical interactions between cancer cells and surrounding environment thereby permitting the expression of the biological tumor nature in terms of growth rate, morphology and differentiation, metastasis, and tumor cell sensitivity to therapies.

Based on surgical breast tumor cell inoculation into the fourth mammary fat pad of immunocompetent mice, our syngeneic orthotopic 4T1 breast tumor-bearing mouse model, which is an aggressive model of human breast carcinoma, has indeed many characteristics that make it a suitable experimental tool for human breast cancer. In addition to their poor immunogenicity – a characteristic shared with human mammary cancers, 4T1 tumor cells are easily implanted into the mammary fat pad thereby allowing for the growth of the primary tumor in the anatomically correct site. Moreover, 4T1 model is capable of spontaneous metastasis to several organs including and not limited to lungs and liver, in a pattern that is analogous to human mammary cancer. Metastases begin while the primary tumor is in place but are heterogenous and not detectable in all animals.

In an interesting way, the model is characterized by the presence of at least two types of tumor-infiltrating immunosuppressive cells – myeloid suppressive cells (MSC) and T regulatory cells (Treg). Such cell populations are known, as a result, to suppress T cell responses and thus promote tumor immune escape and metastasis.

Orthotopic breast tumor model characteristics

 

Our orthotopic syngeneic breast tumor model is a well-suited tool for preclinical testing of new anti-cancer therapies that require an intact immune system to elicit activity, e.g. checkpoint inhibitors or targeted therapies, which would directly target cancer cells or aim at suppressing the immunosuppressive cell functions. Interestingly, our model is run with stable Luc-2-expressing 4T1 tumor cells which has the advantage to monitor tumor growth by in vivo bioluminescence imaging (BLI).

Orthotopic_4T1-Luc_Breast tumor model_bioluminescence

In vivo efficacy and anti-tumor immune response profiling

 

  • 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 an immunotherapeutic treatment reference.
  • Upon study initiation, the model is quickly set up. Weekly reports are provided to follow the progressively achieved efficacy profile of treatments in conjunction with the Sponsor, which allows, if needed, to adjust the experimental design.
Orthotopic_4T1-Luc_Breast tumor model_tumor growth

Our added value

 

  • Longitudinal mice bleeding: blood samples can be collected every week, allowing the evaluation of peripheral markers overtime or at given analysis time-points.
  • 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

contact us

 I agree with the use of my personal data for further communications according to explicyte privacy policy

Explicyte immuno-oncology offers to test novel cancer immunotherapies in an orthotopic syngeneic breast tumor model, well-suited tool for preclinical testing that requires an intact immune system to elicit activity, e.g. checkpoint inhibitors or targeted therapies, which would directly target cancer cells or aim at suppressing the immunosuppressive cell functions. Interestingly, our model is run with stable Luc-2-expressing 4T1 tumor cells which has the advantage to monitor tumor growth by in vivo bioluminescence imaging (BLI).