H2020Индивидуална стипендия2021–2024

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

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2021-12-01 → 2024-04-11
Финансиране от ЕС: 178 320 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Малките екстрацелуларни везикули (екзозоми) се изследват като средство за комуникация между туморните клетки и околната среда при хронична лимфоцитна левкемия. Това помага за разбирането на развитието на болестта и търсенето на алтернативни терапии за пациенти, които не реагират на стандартното лечение.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

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

Chronic lymphocytic leukemia (CLL) is a hematological malignancy characterised by the accumulation of abnormal B lymphocytes in peripheral blood (PB) and lymphoid organs. It represents the most common form of leukemia in the Western hemisphere to affect the elderly, and remains incurable. In the last years, new molecules such as kinase inhibitors were introduced in the standard care of CLL, which partially replaced chemotherapy and antibody-based treatments. These new approaches showed an efficient control of the disease in most cases. However, some patients do not respond or become resistant to current treatments, therefore novel alternative therapies are being continuously developed. The heterogeneous clinical and biological features of CLL position this disease as an attractive, high incidence and easy-accessible sample model for the study of leukemia. The present project is focused on dissecting the cross-talk between small extracellular vesicles (sEV, i.e. exosomes), the CLL tumor cells and the microenvironment (ME), to unravel their role in this disease and explore their therapeutic potential. Small EV are nano-sized vesicles (40-160nm in diameter) originating from the endosome, produced by all cell types and released to the extracellular space. They contain a lipid bilayer and various biomolecules whose composition depends on the parental cell and the physiological conditions in which they were produced. Increasing novel data position sEV as a key and complex cell communication system implicated in several physio-pathological processes. Particularly in cancer, sEV can positively influence disease progression by direct targeting of tumor cells and also by influencing the non-malignant cells that compose the tumor ME. In line with the objectives stated in the 2020 Interim report of the Mission Board for Cancer of the European Commission (EC), this project faces the huge threat that CLL represents for Europe’s citizens and health systems and is positioned within the challenges from the beating cancer plan. We set as main objectives of this project to study the targeting and internalisation of sEV, to study the effects of sEV on immunosuppression and anti-tumor immunity, and to study the effects of sEV on metabolism.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

LUXEMBOURG INSTITUTE OF HEALTH · StrassenКоординаторЛюксембург