Immuno-pharmacology

 

An expert of immune-based targets

To conduct the evaluation of immune-based therapeutic targets, MI-mAbs has a strong expertise in immunopharmacology and cellular immunology. The mechanism of action, the efficacy and safety of the antibody candidates are evaluated on human cells in vitro and then in vivo, in mouse models of human disease. In this context, MI-mAbs can generate antibodies against mouse homologues of the target or genetically-modified mice expressing the human molecule in place of the mouse molecule.

For immunomodulatory antibodies, pharmacologic monitoring in mice is coupled with a very precise analysis of the immune system and its variations under treatment. All of these data are used to determine the ideal therapeutic window for each antibody candidate.

For finely characterizing each candidate antibody (affinity, stability, biochemical profile...) and monitor its evolution in the organism (pharmacokinetics, bioavailability...), Mi-mAbs relies on expertise and cutting-edge technological tools (bio-analytical methods, models of efficacy in vitro and in vivo, flow cytometry, mass spectrometry, ELISA, interferometry of the bilayers...).
The toxicity of candidate antibodies against human targets cannot usually be determined in animal models (usually these antibodies do not cross on the homologous targets in mice). In this context, Mi-mAbs is prepared to :

  • Generate antibodies against murine homologous targets (using these surrogate antibodies, MI-mAbs then evaluates the toxicity of the approach on syngeneic models).

  • Develop, with the help of CIPHE, knock-in mice (in these mice the homologous target, or even the corresponding receptor, is replaced by the human molecule) that could allow direct testing antibody candidate toxicity..

  • Analyze, always in collaboration with CIPHE, immune responses under treatment in depth, in order to validate the mechanism of action of its immunotherapies alone or in combination.

In oncology, the efficacy of the antibody candidates is evaluated on xenogeneic  models (immunodeficient mice in which cell lines of human tumors have been established ). In partnership with the CRCM, Mi-mAbs also tested the effectiveness of antibody candidates on PDX models (Patient Derived Xenograft) of breast cancer, myeloid or acute lymphoid leukemia. These models of mice grafted with patients' tumors are more representative of human tumors than tumor lines.

At last, the platform uses proven predictive models (pathophysiological models in immunocompetent animals) for evaluating immunomodulatory antibodies. MI-mAbs has successful syngeneic tumor models in B6 mice (MC38, B16, GL26 ...) or BALB (CT26 ...): data derived from these models have not only allowed to demonstrate preclinical of anti PD1 and CTLA4 antibodies but they have also been reproduced in humans.