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European Commission
This project has received funding from the
European Union’s Seventh Framework Programme
for research, technological development and demonstration.
agence de communication Lyon
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Objectives of the TumAdoR project

Based on the broad immuno-suppression and strong tumour promotion (proliferation and dissemination) exerted by Adenosine (Figure 1), therapeutic strategies aimed at inhibiting Adenosine are highly promising.

Given the role involvement of the four specific Adenosine receptors involved, the blockade of the enzymatic function of CD73, the sole 5' ecto-nucleotidase expressed at the membrane surface membrane, through neutralizing mAbs, will avoid dephosphorylation of AMP into Adenosine (Ado) (Figure 2)

 

This represents an attractive, potent and safe strategy for the development of innovative immunotherapy.

 

The project aims at paving the way to first-in-human clinical trials of potent neutralizing anti-CD73 mAb candidates in cancer patients. It will validate a novel cancer immunotherapy approach that will

be applicable to a wide range of cancers,
enable the development of specific anti-tumour immune response stopping cancer progression and dissemination,
prevent relapse through restoration of anti-tumour immune memory.

Figure 1

Different impact of Adenosine on immune and stromal cells

 

Figure 2

Extracellular ATP metabolism: CD73 activity is virtually irreversible thus representing a crucial checkpoint in conversion of pro-inflammatory ATP into immunosuppressive Adenosine

Figure 3

CD73 detection by immunohistochemistry in human tumours


At its conclusion TumAdoR project will generate:

New knowledge on CD73 as an immune check point blocker
New preclinical models to evaluate drug candidates blocking CD73 pathway and assess safety of this strategy
Humanized efficient neutralizing anti CD73 mAbs
Companion diagnostic to assess CD73 expression and identify patients eligible for anti CD73 mAb clinical trial
Immuno-monitoring tools to follow relevant immune parameters in patients’ blood during treatment to evaluate its biological efficacy