2016
DOI: 10.1182/blood.v128.22.2127.2127
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A Novel Bcma-Specific, Centyrin-Based CAR-T Product for the Treatment of Multiple Myeloma

Abstract: Chimeric-antigen receptor (CAR)-T cell immunotherapies have been remarkably effective in treating acute lymphoblastic leukemia. However, current strategies generally suffer from difficult, inefficient and costly manufacturing processes, significant patient side effects and poor durability of response in some patients. Here, we report for the first time a CAR-T cell therapeutic comprising a non-immunoglobulin alternative scaffold Centyrin molecule (a "CARTyrin") manufactured with a novel non-viral piggyBacTM (P… Show more

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Cited by 32 publications
(17 citation statements)
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“…In addition to the trials described here, other trials of anti-BCMA CAR-T cells [ 30 ], including three in combination with other CAR-T cells, have been opened since March 2018. Initial data are expected by late 2018 or early 2019.…”
Section: Discussionmentioning
confidence: 99%
“…In addition to the trials described here, other trials of anti-BCMA CAR-T cells [ 30 ], including three in combination with other CAR-T cells, have been opened since March 2018. Initial data are expected by late 2018 or early 2019.…”
Section: Discussionmentioning
confidence: 99%
“…First, the targeting moieties of the CAR often display reduced stability and are therefore at risk of oligomerization or clustering, leading to continuous off-target signaling and development of an exhausted T-cell phenotype ( 142 ). While it is yet controversial whether the choice of a defined co-stimulatory domain can reverse CAR tonic signaling ( 142 144 ), an attractive option to reduce the likelihood of CAR oligomerization or clustering is the use of alternative targeting moieties, such as centyrinsTM, small monomeric proteins based on a consensus tenascin fibronectin domain ( 145 ). One such centyrinTM-based CAR T-cell product is the P-BCMA-101 currently under clinical investigation (NCT03288493) ( 59 , 60 ).…”
Section: T-cell Directed Strategies To Improve Persistency Potency Amentioning
confidence: 99%
“…To further improve on this fusion approach, Centyrin monobodies were integrated into a CARTyrin expression system which combines selection markers and a safety self-killing switch into a simple mRNA and plasmid DNA transcription system [95]. CARTyrins have been generated for targeting Multiple Myeloma [95] showing effective elimination of tumours in head-to-head trials against scFv-based CAR-T therapies, with targeting of prostate cancer also raised as a possible indication for treatment [96]. The Multiple Myeloma CARTyrin was presented as passing safety and efficacy endpoints in a phase 1 trial [97].…”
Section: Combining Monobodies With Antibodiesmentioning
confidence: 99%