PVR-Centered Tumor Membrane Complexes Integrating Immune Modulation, Adhesion, Signaling, and Proteolysis
Project title: PVR-Centered Tumor Membrane Complexes Integrating Immune Modulation, Adhesion, Signaling, and Proteolysis
Acronym: PVR-CORE
Call title: Research Projects
Call code: IP-2026
Funding source: Croatian Science Foundation
Applicant name: University of Rijeka, Faculty of Medicine, Prof. Dr. Tihana Lenac Roviš, PhD
Coordinator: Prof. Dr. Tihana Lenac Roviš, PhD
Research Team, University of Rijeka Faculty of Medicine:
- Nives Jonjić, MD, PhD
- Assoc. Prof. Vanda Juranić Lisnić, PhD
- Prof. Hermann Altmeppen, PhD
- Mijo Golemac, MD, PhD
- Ema Bellulovich, MSc, PhD student
Project implementation period: 01.10.2026 – 30.09.2029
Total project value: EUR 194.000,00
Brief description:
PVR (poliovirus receptor, CD155) is an immune checkpoint ligand overexpressed in solid tumors. An antibody developed by the applicant has completed a phase I clinical trial, demonstrating that targeting PVR can safely activate anti-tumor immunity. Beyond immune regulation, PVR acts as a central organizer of molecules at the tumor cell surface, coordinating adhesion, growth signaling, and immune evasion. Current therapies target these components individually, but tumors often adapt and escape.
This project proposes a shift from single-molecule inhibition to targeting PVR-centered membrane complexes as functional units. It will investigate complexes involving growth factor receptors (EGFR, MET, IGF1R), integrins (αV-containing heterodimers), and ADAM proteases (primarily ADAM17). Using breast cancer, lung cancer, and glioblastoma models, the project will map the composition, localization, and dynamics of PVR-containing complexes in vitro. Functional perturbation with anti-PVR antibodies, growth factor stimulation, and clinically relevant inhibitors will assess effects on signaling, migration, and immune modulation, with in vivo validation in humanized mouse models.
Based on mechanistic insights, biparatopic anti-PVR antibodies will be engineered to destabilize membrane clusters while preserving immune checkpoint blockade. In parallel, exploratory PVR-anchored bispecific antibodies will be evaluated for modulation of tumor signaling and resistance mechanisms.
Conceptually, this project extends immune checkpoint therapy by targeting membrane organization rather than single signaling pathways. Methodologically, it integrates antibody engineering, tumor immunology, and membrane protein biology. The expected outcome is broadly applicable knowledge on tumor surface organization, with translational potential for next-generation antibody-based cancer therapies.
