Antibodies against RCC
A close collaboration between urological surgeons and scientists at the Leiden University Hospital led to the discovery of an antibody, called G250, which reacts with renal cell carcinomas but not with normal kidney cells. Of the normal tissues tested, this G250 antibody only reacts with gastric mucosal cells and bile ducts. Therefore, this antibody has a high tumor specificity and low reactivity with normal tissues.

In in vitro perfusion studies using whole kidneys removed from patients with renal cancer the G250 antibody showed strong reactivity against the tumors. Biodistribution studies in tumor-bearing mice were also extremely positive and showed a high specificity for RCC with only limited reactivity with other types of cancer. In early Phase I studies to determine the maximum tolerated dose using the murine antibody, no evidence of immediate toxicity was seen although some short term, reversible liver toxicity was noted. As expected the murine antibody was seen as a foreign substance by the immune system of the patients, leading to the development of antibodies against the murine G250. To reduce this affect the murine antibody was chimerized to make it 75% human G250 antibody. The chimeric antibody showed similar biodistribution and specificity but was not antigenic in humans. The chimeric form of G250 was constructed by Centocor and was later licensed to Wilex. To date, G250 has completed Phase I clinical trials i




n which it has shown excellent localization in renal tumors. Initial results from early Phase II trials have indicated that radiolabelled G250 antibody can deliver tumor sterilizing radiation doses directly to RCC tumors.
Wilex has entered into a Research and Development agreement with the Ludwig Institute for Cancer Research, New York, to develop antibody G250 as a novel treatment for renal cancer. Phase I and II clinical trials are currently underway with both radiolabelled and non-radiolabelled antibody to develop effective therapeutic regimens for both late stage and early stage RCC, respectively. Results to date are promising. Wilex aims to realise the promise of an effective therapy for RCC before 2004.