Drug intelligence / Profile preview

P56-TCR-engineered T cells

Development stage
Preclinical
Lead developer
IRCCS Ospedale San Raffaele
Modality
TCR-Engineered T Cells → Engineered T Cells → Adoptive Cell Transfer → Cell Therapies, Gene Therapies
Administration
Intravenous
01

Overview

P56-TCR-engineered T cells are an experimental adoptive cell therapy developed by the IRCCS San Raffaele Scientific Institute for the treatment of acute myeloid leukemia (AML). The therapy consists of T cells genetically modified via lentiviral transduction to express the P56 T-cell receptor (TCR), which specifically targets Cathepsin G (CTSG). CTSG is a serine protease overexpressed in AML blasts and leukemic stem cells, where it is aberrantly presented on HLA class I molecules. A unique feature of the P56-TCR is its dual HLA restriction, allowing it to recognize CTSG peptides presented on either HLA-A*24:02 or HLA-C*07:02, which collectively cover a significant portion of the patient population. To optimize functionality and safety, the cells undergo CRISPR/Cas9-mediated knockout of the endogenous TCR to prevent chain mispairing and are further engineered to express the CD8αβ co-receptor. Preclinical studies have demonstrated potent antitumoral activity and disease eradication in AML models with a favorable safety profile.

Other names
P56-TCR T cellsP-56-TCR T cellsP 56-TCR T cellsCTSG-specific TCR-engineered T cells
02

Targets

CTSG/HLA-C*07:02 (Cathepsin G–derived peptide presented by HLA-C*07:02)pMHC-I (Peptide–MHC class I complex)

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