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Development of very promising humanized therapeutic mAbs efficiently neutralizing a novel immunosuppressive pathway involved in a wide range of cancers (TumAdoR)
Date du début: 1 sept. 2013, Date de fin: 31 août 2017 PROJET  TERMINÉ 

Studies have demonstrated the importance of CD73 in the spread of cancer. Overexpressed in numerous cancer types, this enzyme leads to the production of high amounts of extracellular Adenosine, creating an immunosuppressive microenvironment, and contributing to tumor proliferation and dissemination. Neutralizing its activity represents a highly potent and innovative therapy.Following on the recent success of mAbs targeting immune checkpoint (PD1, CTLA4), TumAdoR aims to discover, characterize and produce humanized anti-hCD73 mAbs that will be assessed for their efficacy and safety in relevant mouse preclinical tumor models. It will result in the development of anti-CD73 drug candidates that will strengthen the immune system, stop cancer cell progression and prevent relapse through restoration of immune memory. TumAdoR aims at paving the way to first-in-human clinical trials of potent mAb candidates, and validating a new cancer immunotherapy, suitable for a wide range of cancers.More precisely, TumAdoR will:•Reinforce knowledge about CD73 role as an immune checkpoint target•Correlate CD73 expression with clinical outcome and validate the tumor patients most likely to benefit from CD73 blockade•Discover and develop mAbs neutralizing hCD73•Develop relevant preclinical tumor models to validate the in vivo efficacy and safety of anti-CD73 mAbs candidate(s)•Develop and standardize tools to assess CD73 expression, and monitor immune parameters in patientsTumAdoR addresses topic 1 by developing antibodies neutralizing CD73, and topic 3 by fighting against immune evasion in tumor host microenvironment. The high-level consortium including 3 SMEs possesses all the scientific and clinical expertises, industrial competences, biological and enzymatic assays, biological and clinical resources, and preclinical models to discover and produce mAbs, and investigate the functions of CD73, and the therapeutic impact of its neutralization.

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