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CD19-CAR T cells with multiplexed shRNA

Development stage
Preclinical
Lead developer
Celyad Oncology
Modality
CAR-T Cells → Engineered T Cells → Adoptive Cell Transfer → Cell Therapies, Viral-delivered RNAi → In Vivo RNAi → Gene Silencing → Gene Therapies, RNA Therapeutics → Nucleic Acid Therapeutics
Administration
Intravenous
01

Overview

CD19-CAR T cells with multiplexed shRNA is an allogeneic chimeric antigen receptor (CAR) T-cell therapy that utilizes a single retroviral vector to co-express a CAR targeting CD19 along with multiple short-hairpin RNAs (shRNA). Developed by Celyad, this non-gene-edited approach enables the concurrent knockdown of several genes to optimize the T-cell's therapeutic profile for "off-the-shelf" use. The multiplexed shRNA targets include CD3ζ to prevent Graft-versus-Host Disease (GvHD) by reducing T-cell receptor expression, beta-2-microglobulin (B2M) to minimize HLA class I expression and evade host immune rejection, CD52 to allow for the use of anti-CD52 lymphodepletion, and diacylglycerol kinase alpha (DGKA) to enhance T-cell metabolic activity and persistence. This platform aims to provide a scalable treatment for B-cell malignancies by overcoming the limitations of autologous CAR-T therapies and the complexities of traditional gene-editing techniques like CRISPR.

Other names
CD19-CAR T cells with multiplexed shRNACD-19-CAR T cells with multiplexed shRNACD 19-CAR T cells with multiplexed shRNAshRNA-based allogeneic CD19 CAR-T
02

Targets

DGKA (Diacylglycerol kinase alpha)CD19 (B lymphocyte antigen CD19)B2M (Beta-2-microglobulin)CD52 (CD52 Antigen)T-cell surface glycoprotein CD3 zeta chain mRNA

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