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001     343551
005     20230827173429.0
024 7 _ |a G:(EU-Grant)101098331
|d 101098331
|2 CORDIS
024 7 _ |a G:(EU-Call)ERC-2022-ADG
|d ERC-2022-ADG
|2 CORDIS
024 7 _ |a corda_____he::101098331
|2 originalID
035 _ _ |a G:(EU-Grant)101098331
150 _ _ |a Targeting of glycosylation pathways to empower CAR-T therapy of solid tumors.
|y 2023-07-01 - 2028-06-30
372 _ _ |a ERC-2022-ADG
|s 2023-07-01
|t 2028-06-30
450 _ _ |a GlycoCAR
|w d
|y 2023-07-01 - 2028-06-30
510 1 _ |0 I:(DE-588b)5098525-5
|a European Union
|2 CORDIS
680 _ _ |a Chimeric Antigen Receptor (CAR) T cell therapy uniquely can provide life-long protection against tumor re-emergence upon clearance of even advanced-stage leukemia. However, for the more frequent solid tumor types (carcinomas, lymphomas), clearance of advanced-stage tumors, and especially the subsequent long-term protection, is only rarely achieved. The main reason for this is the multi-pathway immunosuppressive environment that these tumors evolve to overcome the selective pressure imposed by the patient’s immune system. This both hampers the initial attack by CAR-Ts, and often leads to low numbers of long-term persisting CAR-T cells, which tend to be in a state of functional exhaustion. Most attempts at overcoming this, target particular CAR-T cell proteins involved in individual pathways of immunosuppression. However, it is clear from early-stage clinical trials with such engineered CAR-T cells that multiple pathways will need to be tackled at the same time. Inspired by this challenge, I have chosen a radically different path: we are targeting the CAR-T cell glycocalyx, i.e. the assembly of glycosylated structures that forms the outer layer of the cell. The unique property of glycosylation pathways is that they often modulate a large range of cell surface receptor biology at the same time. Excitingly, this new research line has now generated the first highly promising results with the discovery of a single CAR-T glycogene inactivation that results in robust clearance of a benchmark highly immunosuppressive carcinoma rechallenge, in mice that were CAR-T cured from their primary tumor months earlier. Encouraged by these exciting results that demonstrate strong long-term functional persistence of these glyco-engineered CAR-T cells, we have defined a programme to build on this finding and to explore a candidate set of further glycosylation engineering concepts in CAR-T cells, to further improve CAR-T therapy of solid tumors.
909 C O |o oai:juser.fz-juelich.de:1012911
|p authority:GRANT
|p authority
909 C O |o oai:juser.fz-juelich.de:1012911
980 _ _ |a G
980 _ _ |a CORDIS
980 _ _ |a AUTHORITY

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Marc 21