Antibody therapy in renal cell carcinoma.

Contains fulltext : 69826.pdf (publisher's version ) (Open Access)The treatment of metastasized renal cell carcinoma (RCC) still represents a formidable challenge, despite the development of small molecule, tyrosine kinase inhibitors (TKI) that have made a major impact on the disease. Although the percentage of patients achieving a partial response or stabilization of disease has been impressive, these effects are mostly non-durable. Additionally, drug-related side effects can be quite severe. Alternative treatment modalities might be monoclonal antibodies (mAbs). mAbs against RCC-associated antigens have been developed and have shown promise. Additionally, current efforts focus on Bevacizumab that recognizes vascular endothelial growth factor (VEGF). VEGF overexpression in RCC provides the opportunity to inhibit this proangiogenic pathway. Also with Bevacizumab, promising results have been obtained, particularly in combination with other treatment modalities. It is likely that mAbs, either as single agents or in combination with other agents, may become useful additions to the armamentarium to diagnose and treat RCC

A phase II trial of chimeric monoclonal antibody G250 for advanced renal cell carcinoma patients.

Contains fulltext : 57114.pdf (publisher's version ) (Closed access)Chimeric monoclonal antibody G250 (WX-G250) binds to a cell surface antigen found on >90% of renal cell carcinoma (RCC). A multicentre phase II study was performed to evaluate the safety and efficacy of WX-G250 in metastatic RCC (mRCC) patients. In all, 36 patients with mRCC were included. WX-G250 was given weekly by intravenous infusion for 12 weeks. Patients with stable disease (SD) or response were eligible to receive additional treatment for 8 weeks. None of the 36 enrolled patients experienced any drug-related grade III or IV toxicity. Only three patients had grade II toxicity possibly related to the study medication. In all, 10 patients had SD and received extended treatment. One complete response and a significant regression was observed during the follow-up of the treatment. Five patients with progressive disease at study entry were stable for more than 6 months after study entry. The median survival after treatment start was 15 months. The weekly schedule of WX-G250 was well tolerated. With a median survival of 15 months after the start of this treatment and two late clinical responses, WX-G250 seems to be able to modulate mRCC. To improve the activity of WX-G250-specific antibody-dependent cellular cytotoxicity and the clinical response rate, currently combinations of WX-G250 with cytokines are in phase II trials