dhuVHH6-PE-LR

dhuVHH6-PE-LR is an experimental recombinant immunotoxin designed for the targeted treatment of CD7-positive hematologic malignancies, specifically T-cell acute lymphoblastic leukemia (T-ALL). It is a fusion protein consisting of a humanized divalent nanobody (VHH) that specifically binds to the CD7 antigen, fused to a truncated and protease-resistant form of *Pseudomonas* exotoxin A (PE-LR). The PE-LR component is engineered by deleting the majority of domain II (except for the furin cleavage site) and region Ib to reduce lysosomal degradation and enhance the delivery of the cytotoxic domain III to the cytoplasm. Upon binding to CD7 on the surface of malignant T-cells, the immunotoxin is internalized via receptor-mediated endocytosis. The toxin then catalyzes the ADP-ribosylation of elongation factor 2 (EF-2), halting protein synthesis and inducing apoptosis. Despite its rational design for improved stability and reduced immunogenicity, pre-clinical studies in mouse models indicated that dhuVHH6-PE-LR had disappointing in vivo antitumor efficacy compared to its PE38-containing counterpart.

Other names

humanized divalent anti-CD7 nanobody-PE-LR immunotoxin