Chemoimmunoconjugates with the monoclonal antibody 138H11 for targeting the cytotoxic prodrug calicheamicin 0 to renal cell carcinomas

Renal cell carcinomas (RCC) are highly resistent to conventional chemothera py. The monoclonal antibody 138H11 was developed against human gamma-glutam yltransferase as a marker for RCC. This antibody strongly reacts with over 98% of both clear cell and papillary RCC, which together account for over 8 5% of the malignant renal tumours, Extracorporeal perfusion of human kidney s revealed a specific tumor uptake. The cytotoxic agent calicheamicin theta (Cam theta) belongs to the chemical group of enediynes which are DNA cleav ing molecules that show very potent anti-cancer activity, To target the cyt otoxic agent in RCC, we produced chemoimmunoconjugates of mAb 138H11 and Ca m theta with a biocleavable linker and then tested this conjugate on the RC C cell line Caki-2. This novel conjugate was active and released the drug f rom the mAb under the assay conditions. Loss of toxicity through conjugatio n was tolerable. The 138H11-Cam theta conjugates were up to four logs more toxic for RCC than conventional cytostatic drugs.