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Content archived on 2024-06-18

Understanding and manipulating Antibody Dependent Cell Cytotoxicity (ADCC) by human Natural Killer (NK) cells

Objective

High-resolution microscope images of immune cells contacting other cells have revealed temporary membrane structures, often called immune synapses (IS). Proteins commonly segregate into specific regions at the contacts between cells, and exploring how such changing arrangements of proteins occur and how they control immune cell communication is the new science opened up by the immune synapse concept. Over the last decade the use of monoclonal antibodies has revolutionised the treatment of severe human diseases, such as non hodgkins lymphoma (NHL) and rheumatoid arthritis (RA). One way that these antibodies work is by triggering Natural Killer cells to directly kill diseased target cells. Typically antibodies have been used to either block ligand receptor interactions or to evoke antibody effector function and kill malignant target cells by antibody-dependent cell cytotoxicity (ADCC). Crucially, nobody has yet determined what happens at IS when antibodies trigger killing of diseased cells. Through this project we will focus our research to improve our basic understanding of the molecular dynamics that occur during ADCC and to investigate antibodies specifically engineered to enhance ADCC. Here, we plan to use state-of-the-art technologies to image IS during antibody-mediated killing with a view to learning how to best optimize antibodies for this function. Specifically, the spatial relationship and segregation of proteins at the submicrometer scale will be determined during ADCC and compared for the different antibodies and model systems developed. This will establish what determines the efficiency of ADCC and will facilitate the rational design of modified antibodies for optimal medical use. This project will benefit from the knowledge and experience in imaging and cell biology techniques gained by the researcher during her initial training. It will also provide the researcher with invaluable new experience adding to her career development.

Fields of science (EuroSciVoc)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2010-RG
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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MC-ERG - European Re-integration Grants (ERG)

Coordinator

IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
EU contribution
€ 37 500,00
Address
SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
SW7 2AZ London
United Kingdom

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Region
London Inner London — West Westminster
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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