Toxin-Based Therapeutic Approaches

Shapira, Assaf; Benhar, Itai

Lewis Y (Le Y ), a type 2 blood group related oncofetal carbohydrate antigen is expressed on nearly 70% of human epithelial carcinomas [195] [196] [197] . The LMB-1 immunotoxin consists of the anti-Lewis Y monoclonal antibody B3 [198] conjugated to PE38. In a Phase I clinical trial, the immunotoxin was tested on 38 patients with Le Y expressing carcinomas of breast, ovarian, colon, esophagus, stomach and ampulla of Vater. A complete remission was observed in a patient with metastatic breast cancer and a greater than 75% tumor reduction was observed in a colon cancer patient following systemic administration of the immunotoxin. The major toxicity was vascular leak syndrome ascribed to endothelial damage, probably due to binding of the B3 antibody to Le Y antigen which is present in small amounts on endothelial cells [199] . Later developments of Lewis Y targeted toxins produced the recombinant immunotoxins B3(Fv)-PE38 (LMB-7), B3(dsFv)-PE38 (LMB-9) and BR96-Fv-PE40 (SGN-10) which were clinically evaluated in patients with Lewis Y-expressing malignancies. However, no significant antitumor activity was observed in these trials [10, 200] .