Artificial intelligence based miniprotein design to target immunosuppression in cancer
HU-rizont project
2024-1.2.3-HU-RIZONT-2024-00003
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Consortium Partners
The HU-RIZONT project is carried out by an international consortium of leading research institutions, working together to develop innovative miniprotein-based solutions for targeted immunosuppression in cancer.
Frequently Asked Questions
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What is our research topic?
We develop artificial intelligence-guided nanobody-like miniproteins (NLPs) to selectively modulate LILRB4, a key immune checkpoint receptor involved in immunosuppression. By modulating its protein-protein interactions and influencing its signaling activity, we aim to restore immune function, particularly in colorectal cancer.
Why is this important?
Immunosuppression plays a crucial role in cancer progression and treatment resistance. Targeting LILRB4 may enable more effective immunotherapy, and our human cell-based system offers an ethical and clinically relevant alternative to animal models.
What do we want to achieve?
✔️ Design NLPs that inhibit LILRB4
✔️ Identify small molecules that stabilize its multimeric form
✔️ Build and validate a patient-derived organoid model representing the tumor microenvironment
✔️ Create a publicly available toolkit and structural database for broader applications in immunology and oncology
What is new in our approach?
We combine conformation-specific AI-based protein design with molecular modeling, surface display, and a novel co-culture organoid system. This integrative pipeline allows us to test therapeutic strategies in a clinically relevant, human model of colorectal cancer.
Why our team?
Our interdisciplinary consortium includes:
Dr. Tamás Hegedűs (Semmelweis University), expert in transmembrane protein modeling and 3D-bioinformatics; Zoltán Wiener – organoids, Ágnes Enyedi – membrane transport (Semmelweis University)
Prof. Gergely Lukács (McGill University), Fellow of the Royal Society of Canada and specialist in protein quality control
Prof. Giovanni Marzaro (University of Verona), medicinal chemist with strong background in structure-based drug design
Together with young researchers, PhD students, and postdocs, we combine AI, structural biology, pharmacology, and organoid technology to tackle immunosuppression in cancer from multiple directions.