Targeting the vascular-immune interface to induce anti-tumor immunity

Projektbeschreibung

Tumorgefäße für eine verbesserte Immuntherapie anvisieren

Blutgefäße in Tumoren liefern nicht nur Nährstoffe und Sauerstoff, sie regulieren auch die Bewegung und Aktivierung von Immunzellen. Die Schnittstelle ist entscheidend, da sie steuert, wie Immunzellen, z. B. T-Zellen, in der Tumorumgebung rekrutiert und aktiviert werden. Ziel des ERC-finanzierten Projekts VASC-IMMUNE ist es, die Wechselwirkungen zwischen Gefäßen und Immunsystem zu optimieren, um die Immuntherapie zu verbessern, denn trotz der Fortschritte profitieren viele betroffene Personen noch immer nicht davon. Das Forschungsteam wird Vektoren mit Adeno-assoziierten Viren entwickeln, die den Tumor anvisieren, um Immunknotenpunkte um die Blutgefäße des Tumors herum zu schaffen und so die Immunantwort zu verstärken. Durch die Kombination von Fachwissen in den Bereichen Gefäßbiologie, Tumorimmunologie und Gentherapie lautet das Projektziel, bahnbrechende Fortschritte in der Krebsbehandlung zu erzielen.

Ziel

In this ERC Synergy Grant, we will characterize the vascular-immune interface in melanoma and glioblastoma and explore the perivascular niche as a site for local anti-tumor immune activation.
Cancer immunotherapy has made tremendous progress in the last two decades, but a vast majority of cancer patients do not benefit from this progress yet. Refinement of established immunotherapies will undoubtedly increase response rates. However, conceptually brave new therapies must be developed to make additional breakthroughs.
The tumor vasculature plays a key role in orchestrating anti-tumor immunity by regulating recruitment and activation of T-cell and other immune cells. We propose to make a detailed characterization of vascular immune landscapes in melanoma and glioblastoma and to utilize this to optimize vascular-immune crosstalk and immune response as a new breakthrough immunotherapy.
This proposal builds upon new knowledge on how immune hubs can form around tumor vasculature, which to a large part is based upon novel findings and development by the applicants (1, 2) on the importance of perivascular antigen-presenting niches in activating, sustaining, and executing CD8 and CD4 T-cell-mediated immune attacks on cancer. We will develop tumor vessel targeting AAV vectors that can enable therapeutic induction of immune hubs in cancer. This new form of immunotherapy will be evaluated alone and in combination with established cancer immunotherapies.
Combined, our research teams are in a unique position to achieve this goal. Synergistic advancements will be obtained by joining Dimberg’s expertise in the vascular and immune microenvironment in tumors (especially glioblastoma); Tüting’s expertise in tumor immunology and cell plasticity (especially melanoma); and Essand’s expertise in translational gene therapy and cancer immunotherapy. The project is timely, and if successful can bring immunotherapy to the next level, rendering new hope to millions of cancer patients.