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Triad of Precision: A Synergistic 3dCAR-MSC Platform Targeting Melanoma via Immune Activation, TRAIL-induced Apoptosis, and PD-L1 Identification/Blockade

 

BASIC DATA OF THE RESEARCH PROJECT

  • ARIS CODE: L3-70150

  • TITLE: Triad of Precision: A Synergistic 3dCAR-MSC Platform Targeting Melanoma via Immune Activation, TRAIL-induced Apoptosis, and PD-L1 Identification/Blockade

  • PRICE CLASS: D

  • LEADING RESEARCHER: Prof. Urban Švajger, PhD

  • PROJECT LEADER AT INSTITUTE OF ONCOLOGY: Sr. Res. Assoc. Asst. Prof. Urska Kamensek, Ph.D. (Biol.)

  • LEADING ORGANIZATION: Slovenian Institute for Transfusion Medicine

  • PARTICIPATING ORGANISATION: Institute of Oncology Ljubljana

  • DURATION: 1. 3. 2026—28. 2. 2029

  • FINANCING: Slovenian Research and Innovation Agency

 

SHORT SUMMARY

Melanoma is an aggressive skin cancer with a pronounced ability to evade immune surveillance, develop resistance, and immunosuppressive tumor microenvironment, and despite the progress of immune checkpoint inhibitors, outcomes in many patients are still unsatisfactory. The project proposes an innovative, multidimensional therapeutic platform 3dCAR-MSC, based on genetically modified mesenchymal stromal stem cells. MSCs will express CAR targeting PD-L1, surface TRAIL for selective induction of tumor cell apoptosis, and cytokines IFN-γ and IL-12 for activation of endogenous immunity and enhancement of T cell cytotoxicity. The synergistic design is expected to simultaneously address three key obstacles to melanoma treatment: immune escape, resistance to apoptosis, and immunosuppressive TME, while reducing off-target effects compared to more aggressive platforms (e.g., CAR-T). The research plan includes plasmid construction (WP1), optimization of MSC electroporation (WP2), in vitro functional validation (WP3), and in vivo efficacy and safety assessment in mouse melanoma models (WP4). Preliminary data confirm the feasibility of: efficient tumor targeting, cytokine production, apoptosis induction, and robust electroporation protocols with preserved MSC viability.