Human Antibody-enabled Cardiovascular Personalized Theranosis

Introduction

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.

Objectives

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 reprogram an unbalanced functional state toward atheroprotection.

Methodology

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. The following methods will be employed:

1. Pioneering in vivo and in vitro phage display approaches to identify relevant HuAbs (UBx).
2. Multispectral mapping and MacroScreen to unravel the functionomics of MoMP subsets in atherosclerosis (MUNC).
3. Unvisited in silico and biochip development to identify HuAb targets (MAbS, CNRS-TBI).
4. Innovative HuAb bioengineering techniques (CNRS-BacFly and UBx-INP, BTM).
5. Derivatization and labeling to develop PET tracers.
6. Exploring the feasibility of a translational non-invasive multi-marker PET/MRI system for diagnosis and monitoring (CNIC).
7. Designing bispecific antibodies for an adapted immunotherapy strategy targeted to the appropriate plaque (CNRS-BacFly).

Data Processing

Data processing will integrate multimodal images to obtain insight into plaque morphology and composition (PMI).

Conclusion

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.