Objetivo 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. Programa(s) IC-INTAS - International Association for the promotion of cooperation with scientists from the independent states of the former Soviet Union (INTAS), 1993- Tema(s) 4 - Life Sciences GEORGIA - GEORGIA Convocatoria de propuestas Data not available Régimen de financiación Data not available Coordinador University College London Aportación de la UE Sin datos Dirección Windeyer Institute, 46 Cleveland Street W1P 6DB London Reino Unido Ver en el mapa Coste total Sin datos Participantes (4) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo Oncology Research Centre of Ministry of Public Health Georgia Aportación de la UE Sin datos Dirección Lisi Lake 380077 Tbilisi Ver en el mapa Coste total Sin datos Scientific Research Institute of Haematology and Transfusiology Georgia Aportación de la UE Sin datos Dirección Kazbegi Ave 22 380077 Tbilisi Ver en el mapa Coste total Sin datos Tbilisi State University Georgia Aportación de la UE Sin datos Dirección Chachchavadze Avenue 380028 Tbilisi Ver en el mapa Coste total Sin datos Universita di Genova Italia Aportación de la UE Sin datos Dirección via de Toni 14 16132 Genova Ver en el mapa Coste total Sin datos