Peptide Neo-Epitope-recognizing binding domain (PNE-binding domain) (PNE-binding domain)

The Peptide Neo-Epitope-recognizing binding domain (PNE-binding domain) is the extracellular recognition component of the CLBR001 switchable chimeric antigen receptor (sCAR-T) system [1]. This domain is a synthetic single-chain variable fragment (scFv) engineered to bind with high affinity to a non-immunogenic peptide neo-epitope (PNE), typically a 14-amino acid sequence from the yeast transcription factor GCN4 [2]. In the CLBR001 therapeutic platform, the CAR-T cells do not recognize tumor cells directly; instead, their activity is mediated by a bifunctional adapter molecule, or switch (e.g., SWI019) [3]. The switch molecule acts as a bridge, binding the PNE-binding domain on the T-cell and a specific tumor-associated antigen, such as CD19, on the cancer cell [4]. This interaction forms a stable immunological synapse, triggering T-cell signaling, proliferation, and targeted cytotoxicity against the tumor [1, 2]. The primary advantage of this system is the ability to control the magnitude of the immune response by titrating the dose of the switch molecule, which aims to improve safety by mitigating risks like cytokine release syndrome [1, 3]. CLBR001 is currently being evaluated in clinical trials for patients with B-cell malignancies, including various forms of lymphoma and leukemia [3, 4].

Other names

anti-PNE scFvanti-GCN4 scFv52SR4 scFvCLBR001 CAR binding domainsCAR-T binding domain

The PNE-recognizing binding domain acts as a synthetic receptor on the surface of T-cells that specifically binds to a peptide neo-epitope (PNE) tag on a bifunctional switch molecule [1]. This switch molecule simultaneously binds to a tumor-associated antigen, such as CD19, creating a bridge that facilitates the formation of an immunological synapse between the CAR-T cell and the target cancer cell [2]. This interaction triggers the phosphorylation of intracellular signaling domains, leading to T-cell activation, cytokine production, and the directed lysis of the tumor cell [1, 4].