Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5557651 | Pharmacology & Therapeutics | 2017 | 51 Pages |
Abstract
Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy against hematologic malignancies. Antitumor activity of CAR T cells, however, needs to be improved to increase therapeutic efficacy in both hematologic and solid cancers. Limitations to overcome are 'on-target, off-tumor' toxicity, antigen escape, short CAR T cell persistence, little expansion, trafficking to the tumor and inhibition of T cell activity by an inhibitory tumor microenvironment. Here we will discuss how optimizing the design of CAR T cells through genetic engineering addresses these limitations and improves the antitumor efficacy of CAR T cell therapy in pre-clinical models.
Keywords
CD40Lcytotoxic T-lymphocyte associated protein 4CTLA-44-1BB ligandGvHDPSCA4-1BBLICARPSMAB-ALLCostimulationTregsDCsNFATTAAPD-1PD-L1CRSProstate stem cell antigenProstate specific membrane antigentumor-associated antigeninterleukinGraft-versus-host diseaseTumor-infiltrating lymphocytesTILSDendritic cellsNK cellsNatural killer cellsRegulatory T cellsCytokine Release SyndromeCytokinesNuclear Factor of Activated T CellsCD40 ligandCARProgrammed cell death 1 ligand 1Genetic engineeringTumor microenvironmentprogrammed cell death protein 1chimeric antigen receptor
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Authors
Janneke E. Jaspers, Renier J. Brentjens,