Mechanism
CD19 (B cells) and PD-1+ pathogenic T cells
Assets acting on this target.
- Class
- Allogeneic dual-targeting CAR-Vdelta1 (gamma-delta) T-cell therapy
- Pathway
- Engineered Vdelta1 gamma-delta T cells carrying a CD19 nanoantibody CAR plus a PD-1 nanoantibody module simultaneously deplete CD19+ B cells and PD-1+ pathogenic T cells (Tfh/Tph), disrupting T-B cell collaboration in autoimmune disease
This mechanism uses genetically engineered gamma-delta T cells, a distinct immune cell lineage from the more commonly used alpha-beta T cells, as the chassis for a chimeric antigen receptor (CAR) therapy directed at autoimmune disease rather than cancer. The cells carry two targeting modules: one recognizes CD19, a surface marker expressed broadly across the B-cell lineage, and the other recognizes PD-1, a receptor upregulated on a subset of T cells (follicular and peripheral helper T cells) that drive autoantibody production by providing help to B cells. By eliminating both cell types simultaneously, the therapy aims to interrupt the collaborative loop between helper T cells and B cells that sustains autoreactive antibody production in diseases such as lupus and other systemic autoimmune conditions. Because the platform uses the Vdelta1 subset of gamma-delta T cells, which recognize targets independently of the classical major histocompatibility complex machinery, cells from a healthy donor can potentially be used across many patients without triggering the graft-versus-host reactions that limit off-the-shelf use of conventional T cells. This addresses a practical need in cell therapy: an available, ready-to-use product rather than one manufactured individually from each patient's own cells.
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