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Reprogramming of the leukemic microenvironment by small extracellular vesicles: from characterization to therapeutic application

Project description

Role and therapeutic potential of extracellular vesicles in cancer

Cells communicate with each other through extracellular vesicles, which carry proteins, lipids and RNA. Emerging evidence indicates that extracellular vesicles also play a role in cancer cell proliferation, migration and metastasis. The aim of the EU-funded EVIL project is to investigate the tumour-promoting mechanisms of extracellular vesicles in chronic lymphocytic leukaemia (CLL), a haematological malignancy of B lymphocytes. Researchers will examine the uptake of extracellular vesicles by target cells and study the functional outcome of blocking the process via inhibitors. Particular focus will be given to the contribution of extracellular vesicles to immune system evasion by CLL as well as their therapeutic potential.

Objective

The proposed program, to be developed by Dr Pablo Morande, aims at investigating interactions between chronic lymphocytic leukemia (CLL) B-cells and their microenvironment, with a focus on small extracellular vesicles (sEV). CLL is the most frequent hematological malignancy of the adult in Europe. Despite recent advances in the standard of care, there is still no curative therapeutic option. Small EV represent an important part of the cell-to-cell communication. They play a key role in promoting cancer by influencing multiple tumor-related functions like cellular proliferation, migration, and metastasis; and can also impair an efficient anti-tumor immune response. In this proposal, Dr Morande will study the mechanisms underlying sEV-induced cellular modifications in vivo in the context CLL, using transgenic murine models and patient samples. The host group has proved experience in the field of sEV in cancer and recently deepened into the role of sEV in leukemia development in vivo. The candidate will dissect the mechanisms enabling sEV uptake in various types of target cells in vivo, and test inhibitors or neutralizing antibodies to block the pro-tumoral role of sEV in leukemic mice. He will study the functional impact of sEV on the immune system leading to tumor evasion, focusing on immune checkpoint ligands, and design bioengineered sEV to test them as immunotherapy in preclinical models. Finally, he will focus on sEV understudied cargoes such as metabolites by investigating their occurrence on sEV and the consequences on metabolic activity of target cells, to reveal new directions for the development of innovative therapies. The development of the present proposal will enable Dr Morande to achieve a broad range of new technical and management skills through a variety of multidisciplinary training programs. This will represent a key step for his final objective to become an independent scientist.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

(opens in new window) H2020-MSCA-IF-2020

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Coordinator

LUXEMBOURG INSTITUTE OF HEALTH
Net EU contribution
€ 178 320,00
Address
1A RUE RUE THOMAS EDISON
1445 Strassen
Luxembourg
Region
Luxembourg Luxembourg Luxembourg
Activity type
Research Organisations
Links
Total cost
€ 178 320,00