Objectif B-CLL is the commonest leukaemia in the western world. Treatment, to date, has mostly been the use of chemotherapy, which frequently reduces the tumour load, but eventually resistant tumour cells re-appear in most cases. Antibodies are very specific reagents, which have been used to target a variety of lymphoma and leukaemia cells. Apart from complement activation, antibodies require effector cells to damage tumour cells. Our approach is to optimise the activation of myeloid effectors cells and target them specifically to the tumour cells. We are therefore using bispecific antibodies with one specificity for the FcgRI trigger molecule on monocytes and activated neutrophils and the other specificity for molecules on CLL cells, CD19 and CD5. In order for bispecific antibodies to be effective in CLL patients, both monocyte and neutrophil function must be optimal. There is some evidence that this might be compromised without treatment and certainly is during chemotherapy of CLL patients. Therefore, task 1 is to carry out a detailed analysis of the functions of these natural effectors cells in patients without treatment and following tumour bulk-reducing chemotherapy to assess at what time full myeloid cell function recovers.Experimental analysis on activation and phagocytosis will be carried out in UCL department of Immunology and TSU department of Immunology on the blood from well-documented patients in UCL Hospital and the Institute of Haematology and Transfusiology (IHT) and National Cancer Centre (NCC) in Tbilisi. Task 2 is aimed at optimising the phagocytosis of CLL cells, in vitro, by bispecific antibodies and various cytokines. This will be carried out in the departments of Immunology at UCL and TSU. Phagocytes rapidly take up Apoptosing cells. Therefore, task 3 will be to test the in vitro effects of isoprenoids on CLL cells, since these metabolites of mevalonate have previously been shown to induce apoptosis of leukaemic cells. This will be carried mainly in TSU department of Immunology. There are already strong links between UCL and TSU departments of Immunology through a TEMPUS JEP and teams in Tbilisi are already carrying out 'CLL research'. The existing collaboration will facilitate management of the project and ensure a successful outcome.It is anticipated that the results of this study will allow the development of protocols for clinical trials for bispecific antibody therapy in UCL and IHT and provincial hospitals under the umbrella of the National Cancer Centre in Georgia. Programme(s) IC-INTAS - International Association for the promotion of cooperation with scientists from the independent states of the former Soviet Union (INTAS), 1993- Thème(s) 4 - Life Sciences GEORGIA - GEORGIA Appel à propositions Data not available Régime de financement Data not available Coordinateur University College London Contribution de l’UE Aucune donnée Adresse Windeyer Institute, 46 Cleveland Street W1P 6DB London Royaume-Uni Voir sur la carte Coût total Aucune donnée Participants (4) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire Oncology Research Centre of Ministry of Public Health Géorgie Contribution de l’UE Aucune donnée Adresse Lisi Lake 380077 Tbilisi Voir sur la carte Coût total Aucune donnée Scientific Research Institute of Haematology and Transfusiology Géorgie Contribution de l’UE Aucune donnée Adresse Kazbegi Ave 22 380077 Tbilisi Voir sur la carte Coût total Aucune donnée Tbilisi State University Géorgie Contribution de l’UE Aucune donnée Adresse Chachchavadze Avenue 380028 Tbilisi Voir sur la carte Coût total Aucune donnée Universita di Genova Italie Contribution de l’UE Aucune donnée Adresse via de Toni 14 16132 Genova Voir sur la carte Coût total Aucune donnée
