ABCardionostics · Human Antibody-enabled Cardiovascular Personalized Theranosis

ABCardionostics envisions an innovative multi-marker-based positron emission tomography (PET)/ magnetic resonance imaging (MRI) system for efficient staging and personalized treatment of vulnerable patients with atherosclerosis. To provide a snapshot of plaque composition, along the arterial tree of at-risk patients, human antibodies (HuAbs) targeting different affected arterial sites will be developed. Importantly, HuAbs targeting culprit and protective monocyte/macrophage (MoMP) populations that are instrumental in plaque progression will be crucial to assess disease status and reprogramme an unbalanced functional state toward atheroprotection. To translate this concept into clinical practice, the ABCardionostics consortium will combine cutting-edge biotechnologies and in silico and computing analyses to close the knowledge gaps on plaque MoMP spatiotemporal dynamics and the lack of imaging approaches for multi-marker detection: pioneering in vivo and in vitro phage display approaches to identify relevant HuAbs (UBx), multispectral mapping and MacroScreen to unravel the functionomics of MoMP subsets in atherosclerosis (MUNC), unvisited in silico and biochip development to identify HuAb targets (MAbS, CNRS-TBI), innovative HuAb bioengineering techniques (CNRS-BacFly, and UBx-INP, BTM), derivatization and labelling to develop PET tracers to finally explore the feasibility of a translational non-invasive multi-marker PET/MRI system for diagnosis and monitoring (CNIC) and an adapted immunotherapy strategy targeted to the appropriate plaque by designing bispecific antibodies (CNRS-BacFly). Data processing will integrate multimodal images to obtain insight into plaque morphology and composition (PMI). ABCardionostics successful completion will bring HuAb leads for atherosclerosis theranosis, and novel tools for HuAb identification and design, easily transposable to other diseases, revolutionizing the current imaging and therapeutic approaches.