Bacterial infections account for an estimated 20% of global mortality. Current treatments rely primarily on antibiotics, but their effectiveness is limited by nonspecific effects, difficulty in targeting intracellular bacteria, and the growing threat of antimicrobial resistance. Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of death from a single infectious agent. Multidrug-resistant TB (MDR-TB) poses a critical threat to global health security, with one-quarter of the world’s population carrying latent Mtb infections, many involving resistant strains. Preventing the expansion of this reservoir is a pressing priority. Immunotherapy offers an alternative strategy, though its success depends on the immune capacity of often-compromised hosts.
The long-term vision of NanoBiCar is to transform the treatment of bacterial infections with innovative immunotherapeutic approaches designed to overcome these challenges and extend well beyond TB.
Using TB as a proof of concept, the project will employ universal infection markers to identify Mtb-infected cells and extracellular bacteria, applying three novel immunotherapeutic platforms never before tested in bacterial diseases. mRNAs encapsulated in lipid nanoparticles will be used to generate, in vivo, T cells engineered with chimeric antigen receptors (CAR-T), bispecific T cell engagers (BiTEs), and xenoantigen expression in MICs. These strategies will target and eliminate intracellular bacteria. Importantly, they are designed to be safe, cost-effective, accessible, and ready-to-use — suitable for high-burden, low-resource settings and effective regardless of strain resistance, bacterial niche, host genetics, or immune status.
NanoBiCar will be carried out by a multidisciplinary consortium of internationally recognized institutions and experts, including UPV, CIBER, Centro de Investigación Príncipe Felipe (CIPF), Armando Acosta Domínguez (AAD), Technion–Israel Institute of Technology (TIIT), Maria E. Sarmiento (MES), Victor Paralluelo Santamaría (VPS), CNRS, Leiden University Medical Center (LUMC), TASMC, and IGTP-CERCA (IGTP). Their complementary expertise in cutting-edge technologies will enable the development and evaluation of next-generation immunotherapies for TB.
At CNRS, the team led by Jérôme Nigou — a leading authority on Mtb-lipid presentation by CD1 — will contribute its expertise in Mtb-lipid isolation, characterization, and the generation of CD1–lipid complexes. CNRS will produce CD1:lipid complexes, soluble lipids/ManLAM, CD1-transfected cell lines, assess ligand specificity, and participate in lipid nanoparticle characterization, data analysis, and final reporting.