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TCRabX

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Structural basis for the therapeutic efficiency of optimal affinity T cell recep...

Structural basis for the therapeutic efficiency of optimal affinity T cell receptors Demographic change includes population ageing, and incidence rates begin to increase for many types of cancer in middle-aged and elderly people. Traditional cancer treatment includes surgery, chemotherapy, and radiation therapy, w... ver más

31/07/2022

CHARITE UNIVERSIT...

264K€

Presupuesto del proyecto: 264K€

Líder del proyecto

CHARITE UNIVERSITAETSMEDIZIN BERLIN No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2022-07-31

MSCA-IF-2017: Individual Fellowships

I+D

Cerrada hace 7 años

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

3 Participantes

CHARITE UNIVERSITAETSMEDIZI...

264.11K€ | Lider

MONASH UNIVERSITY

178.38K€ | Participante

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Duración del proyecto: 47 meses Fecha Inicio: 2018-08-03
Fecha Fin: 2022-07-31

Líder del proyecto

CHARITE UNIVERSITAETSMEDIZIN BERLIN No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 264K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Demographic change includes population ageing, and incidence rates begin to increase for many types of cancer in middle-aged and elderly people. Traditional cancer treatment includes surgery, chemotherapy, and radiation therapy, while tumour immunotherapy by T cell receptor (TCR) gene transfer represents an alternative form of treatment. The transfer of tumour-specific TCR genes into patient’s peripheral blood lymphocytes targets cancer specifically and effectively. But while patient-derived low-affinity TCRs do not show therapeutic activity, optimal-affinity TCRs, as isolated from newly-generated antigen-negative humanized mice with a diverse human TCR repertoire, can effectively delay tumour regression. X-ray crystallography is a powerful tool of structural biology, which helps researchers to identify the three-dimensional (3D) structures of biological macromolecules such as TCRs complexed to their cognate peptide-loaded major histocompatibility complex (pMHC) molecules. Recent research uncovered the docking topologies of naturally selected TCRs, but therapeutically efficient optimal-affinity TCRs recognizing tumour-associated self-antigens, have not been analysed to date. The exceptional specificity of TCRs is determined by three complementarity-determining regions (CDRs) of the TCR alpha- and beta-chains. Biomedical research on TCR gene therapy and design of future clinical trials will hugely benefit from the identification of CDR-mediated contact points made between therapeutic TCRs and the pMHC on their target cells. TCRabX is an interdisciplinary research project investigating the 3D structures of 13 TCRs complexed to MHC-I or MHC-II, respectively. It connects innovative clinical immunology research in Berlin/Germany and world-class structural biology research in Melbourne/Australia. The proposed research will enhance the health and well-being of citizens in Europe and worldwide by supporting the advancement of cancer immunotherapy approaches.

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