Drug intelligence / Profile preview

LV169-R-Lck1.3

Development stage
Preclinical
Lead developer
Vyriad
Modality
CAR-T Cells → Engineered T Cells → Adoptive Cell Transfer → Cell Therapies, Lentiviral Vectors → Retroviral Vectors → Viral Vectors → Gene Addition/Replacement → Gene Therapies
Administration
Intravenous
01

Overview

LV169-R-Lck1.3 is an investigational CD3-targeted lentiviral vector platform designed for the *in vivo* generation of CAR T cells. It utilizes a modified VSV-G envelope that has been detargeted from its natural LDL receptor and retargeted to T cells via a CD3-specific single-chain variable fragment (scFv). To address the risk of off-target transduction of malignant cells (such as plasma cells in multiple myeloma) by CAR proteins incorporated into the vector envelope, this construct employs a reverse-orientation transgene driven by a modified human distal Lck promoter (Lck1.3). The Lck1.3 promoter, which includes an inserted TATA box and CMV enhancer, ensures that the CAR transgene is transcriptionally silenced in producer cells and off-target cells but remains highly active in transduced T cells. Preclinical studies in multiple myeloma models have demonstrated that a single intravenous dose of LV169-R-Lck1.3 encoding a BCMA-targeted CAR can achieve complete tumor clearance and generate circulating anti-BCMA CAR T cells.

Other names
LV169-R-Lck1.3 encoding BCMA-CARLV-169-R-Lck1.3 encoding BCMA-CARLV 169-R-Lck1.3 encoding BCMA-CARCD3-targeted lentiviral vector LV169-R-Lck1.3CD-3-targeted lentiviral vector LV169-R-Lck1.3CD 3-targeted lentiviral vector LV169-R-Lck1.3
02

Targets

CD3 (T-cell surface glycoprotein CD3)BCMA (B-cell maturation antigen)

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