Noninvasive Imaging of the Immune Checkpoint LAG-3 Using Nanobodies, from Development to Pre-Clinical Use.

Immune checkpoint inhibition (ICI) is a promising cancer therapy, which has progressed rapidly from a preclinical concept to clinical implementation. Commonly considered targets in ICI are CTLA-4, PD-1/PD-L1, and LAG-3, and the list grows. As ICI is generally only beneficial for a subset of patients, there is a need to select patients that are eligible for therapy as well as to monitor therapy response. There is growing interest to do this noninvasively, by molecular imaging with target-specific tracers. To this day, noninvasive imaging has focused on CTLA-4 and PD-1/PD-L1, while there is no noninvasive tool available to accurately assess LAG-3 expression in vivo. In this proof-of-concept study, we developed nanobodies, the smallest functional fragments from camelid heavy chain-only antibodies, to noninvasively evaluate mouse LAG-3 expression using single photon emission computed tomography (SPECT)/CT imaging. The in vitro characterization of 114 nanobodies led to the selection of nine nanobodies binding to mouse LAG-3. The injection of

Déclaration de conflit d'intérêts

Marleen Keyaerts received travel and accommodation expenses from Bayer; Nick Devoogdt, Sam Massa, Geert Raes are shareholders and consultants of Camel-IDS which develops cancer therapeutics based on radiolabeled nanobodies. Marleen Keyaerts received research funding from Camel-IDS. Quentin Lecocq, Marleen Keyaerts, Karine Breckpot, Geert Raes, Nick Devoogdt has patents on Nanobody imaging and therapy.