Efficient in vivo targeting of malignant melanoma by single-chain Fv antibody fragments

Single-chain antibody fragments (scFvs) have superior pharmacokinetic and b iodistribution characteristics compared with larger antibody fragments when used for radioimaging of human tumours. An scFv specific for malignant mel anoma (B4 scFv) was tested in a mouse xenograft model for human melanoma an d compared with the monoclonal antibody (MAb) LHM2. LHM2 is specific for th e high molecular weight proteoglycan melanoma-associated antigen (HMW-MAA), while B4 scFv binds a novel melanoma specific antigen. The B4 scFv was cle ared rapidly from the circulation (t(1/2)alpha = 7 min) compared with LHM2 MAb (t(1/2)alpha = 37 min). However, the B4 scFv had an unusually long t(1/ 2)beta (437 min compared with 384 min for LHM2 MAb). Biodistribution studie s showed that B4 accumulated specifically in the tumour grafts. Although no n-specific accumulation in the liver, lung, spleen and blood was lower than with LHM2, non-specific accumulation of B4 in the kidney was higher. Despi te this, the overall targeting efficiency in this study, as determined by t umour:normal tissue ratios, showed that B4 was superior to whole antibody. Immunoscintigraphy images showed good correlation with the biodistribution data for B4 and LHM2. This study represents the first use of an anti-melano ma scFv in vivo. (C) 1999 Lippincott Williams & Wilkins.