Acute myeloid leukaemia (AML) is a cancer in the bone marrow, where all the cells that constitute the blood are produced. It is therefore characterised by an abnormal production of blood cells. The immune system protects the organism from pathogens like viruses and bacteria but, also, under normal circumstances, has a very important function in finding and killing abnormal pre-malignant cells. When the immune system is not able to recognise and/or kill these cells, cancer develops. In order to treat patients with AML a combination between retinoic acid and arsenic trioxide has been used for several decades but is associated with high toxicity and limited success. More recently a new approach has been undertaken where immunotherapy (ACT), employing cells from the immune system, has shown some therapeutic value. ACT cell engineering is a very expensive and laborious task not widely available. Here we propose an approach where therapeutic cells are induced in situ (TCIS) using RA+NPs and healthy hematopoietic stem cells (HSCs) as trojan cells, for nanoparticle delivery at the leukemic niche. We expect this TCIS approach to be able to reach the bone marrow and after activation induce anti-leukemic response in the organism. We will use animal models of leukaemia and high-tech image analyses to study the TCIS response against the disease. This project is in line with the 2030 UN Sustainable Development Goals for Good Health and Well-being and it integrates researchers from complementary scientific fields from England and Portugal with the spirit of maintaining an historical partnership between both countries for the good of all.
TROJANLEUK will use NPs as a rheostat for understanding the importance of RA in the BM niche in the context of health and disease. It will directly explore the bipolar nature of RA, with respect to HSC state, inside the BM niche and this has never been investigated.
http://doi.org/10.54499/2022.05946.PTDC
2023-03-01
2024-08-31
49.890,01€
2022.05946.PTDC
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