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T22-PE24-H6 is a self-assembling protein-based nanoparticle developed by Nanoligent for the targeted treatment of CXCR4-overexpressing cancers. The construct is a recombinant fusion protein consisting of three functional domains: a T22 peptide at the N-terminus that serves as a high-affinity ligand for the C-X-C chemokine receptor type 4 (CXCR4); a de-immunized 24 kDa catalytic domain of Pseudomonas aeruginosa exotoxin A (PE24) as the cytotoxic payload; and a C-terminal hexahistidine (H6) tag that triggers the self-assembly of monomers into toroidal nanoparticles of approximately 60 nm. Upon binding to CXCR4 on the surface of cancer cells, the nanoparticle is internalized via receptor-mediated endocytosis. Once in the cytosol, the PE24 domain inhibits protein synthesis by ADP-ribosylating elongation factor 2 (EF-2), leading to apoptotic cell death. This therapeutic candidate is being investigated for its potential in treating hematological malignancies such as Acute Myeloid Leukemia (AML) and Diffuse Large B-cell Lymphoma (DLBCL), as well as solid tumors including Colorectal Cancer and Head and Neck Squamous Cell Carcinoma (HNSCC).
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