IN-VITRO AND IN-VIVO EVALUATION OF STREPTAVIDIN IMMUNOCONJUGATES OF THE 2ND GENERATION TAG-72 MONOCLONAL ANTIBODY-CC49

Streptavidin was conjugated to the second-generation TAG-72 monoclonal antibody CC49 at lysine amino acids, oxidized carbohydrates or reduce d disulfides on the immunoglobulin. The streptavidin immunoconjugates were radiolabelled with In-111-DTPA-biocytin and their immunological c haracteristics evaluated in vitro and in vivo. FPLC analysis showed a single peak (mel. wt>350 kDa) for the lysine conjugate and sulfhydryl conjugate (mel. wt similar to 210 kDa) but multiple peaks (similar to 210 to >350 kDa) for the carbohydrate conjugate. There were only small differences in immunoreactivity against bovine submaxillary mucin in vitro. However, in mice bearing subcutaneous LSI74T tumours, the lysin e conjugate exhibited significantly lower tumour uptake (<2% i.d./g) c ompared to the other streptavidin-CC49 conjugates (10-40% i.d./g) or D TPA-CC49 (14-18% i.d./g). Due to the monomeric nature and smaller mole cular size of the sulphhydryl conjugate, and its similar in vitro and in vivo characteristics compared with DTPA-CC49, this conjugate has be en selected for future pretargeting studies with In-111 and Y-90 bioti n.