Overcoming resistance to immunotherapy: Immunostimulatory tumor-derived extracellular vesicles as multifunctional anticancer agents

Projektinformationen

IMMUNO-TEX

ID Finanzhilfevereinbarung: 101078198

DOI

10.3030/101078198

Das Projekt endete am 1 Juni 2023

EK-Unterschriftsdatum 23 Januar 2023

Startdatum 1 Mai 2023

Enddatum 30 April 2028

Finanziert unter

• European Research Council (ERC)

Gesamtkosten

€ 1 650 778,00

EU-Beitrag

€ 1 650 778,00

Koordiniert durch

KLINIKUM DER TECHNISCHEN UNIVERSITÄT MÜNCHEN (TUM KLINIKUM)
Germany

Periodic Reporting for period 1 - IMMUNO-TEX (Overcoming resistance to immunotherapy: Immunostimulatory tumor-derived extracellular vesicles as multifunctional anticancer agents)

Berichtszeitraum: 2023-05-01 bis 2025-10-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

Tumor immunotherapy with immune checkpoint inhibitors (ICI) has unprecedented therapeutic potential, but its success is limited to a minority of patients with preexisting antitumor T-cell immunity. For patients with poorly-immunogenic tumors, combinatorial immunotherapies are urgently needed. With a vast and bioactive cargo (proteins, lipids, nucleic acids), extracellular vesicles (EVs) have intrinsic property to regulate complex pathways in distant target cells. Even though they can transfer tumor antigens which potentially activate T cells, tumor-derived EVs (TEX) have mainly been associated with immunosuppressive function. I have recently identified innate immune pathways within tumor cells that regulate TEX biogenesis and immunogenicity. This allows for the first time to “force” tumor cells to release a defined immunostimulatory (is)TEX product. The unconventional objective of IMMUNO-TEX was to generate a platform for the pioneering therapeutic use of tumor-derived isTEX as multifunctional cell-free anticancer agents. isTEX combine a cargo of a plethora of patient-specific tumor (neo-) antigens and immunostimulatory constituents within a single, non-toxic delivery vehicle, that allows for efficient priming of tumor antigen-specific T cells. The ability to harness the vast potential of isTEX is directly interwoven with a more detailed mechanistic understanding how tumor-specific cargo packaging in EVs occurs and how they alter immune cell function. Therefore, IMMUNO-TEX was set up to identify and exploit the intracellular machinery in tumor cells for optimal isTEX generation, investigate how isTEX enable an immune-supportive tumor microenvironment, and validate isTEX to overcome ICI resistance in relevant murine and human model systems. Hereby, IMMUNO-TEX aimed to eliminate current limitations of ICI immunotherapy by rationally designed combination with isTEX to allow responsiveness in patients with poorly immunogenic tumors.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

The project was terminated before initiation.
No project-related work was performed.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

The project was terminated before initiation.
No results beyond the state of the arts were generated.