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

Introduction

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.

Background

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.

Role of Tumor Vasculature

The tumor vasculature plays a key role in orchestrating anti-tumor immunity by regulating the recruitment and activation of T-cells 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.

Research Foundations

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.

Development of Therapeutic Vectors

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.

Collaborative Expertise

Combined, our research teams are in a unique position to achieve this goal. Synergistic advancements will be obtained by joining:

1. Dimberg’s expertise in the vascular and immune microenvironment in tumors (especially glioblastoma);
2. Tüting’s expertise in tumor immunology and cell plasticity (especially melanoma);
3. Essand’s expertise in translational gene therapy and cancer immunotherapy.

Conclusion

The project is timely, and if successful, can bring immunotherapy to the next level, rendering new hope to millions of cancer patients.