KQ1 – How can target activity be modulated through antibody binding?

KQ1 – How can target activity be modulated through antibody binding?

(Frédéric Jean-Alphonse, Marie-Alix Poul)

Antibodies recognise their targets with high affinity and specificity, but can sometimes exert modulatory activities through constraints generated at the epitope/paratope interface. Exploring this properties, which hold great opportunities for the development of novel-generation therapeutic antibodies, is the central objective of KQ1.

KQ1 projects focus on the identification and characterization of modulating antibodies, independently from their format.

KQ1 includes three axes on innovative antibodies that modulate pathophysiological target activities in oncology, immunology, reproduction, and central nervous system disorders.

Two axes concern the modulating profile of agonist/antagonist/biased mAbs (axis 1) and the modulation of oligomeric targets (axis 2).

Axis 3 focusses on the development of antibodies that affect the sub cellular trafficking of the target (including antibodies that induce internalization and/or degradation of the target and intrabodies). Besides offering new potential therapeutic antibodies, axis 3 brings knew knowledge on the target physiological and pathophysiological functions.

A general concern of the 3 axes of KQ1 is also to obtain conditional antibodies, i.e. antibodies that exert their function in specific conditions (pH, redox,…) in order to increase the specificity of their targeting in pathological tissues.

Flagship project

Towards therapeutic antibodies with pH-switchable properties