One complete response and a significant regression was observed during the follow-up of the treatment. 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. (IFN-(CR): the disappearance of all known disease determined by two evaluations not less than 4 weeks apart. (2) (PR): ?50% decrease in the sum of products of largest and perpendicular diameters of the lesions that have been measured to determine the effect of therapy by two evaluations not less than 4 weeks apart, in the absence of new lesions or progression of any lesion. (3) (PD): a 25% or more increase in the size of one or more measurable lesions, or the appearance of new lesions. For the CT and MRI evaluations an independent central review was performed as requested by protocol. Statistical methods The study had a two-stage design. In the first stage, 32 evaluable patients with mRCC were included. In all, 22 additional patients were allowed to participate (54 patients in total) if at least three objective responses were observed at the time of the radiological evaluation at week 16. The study had to be terminated if less than three patients or more than five had an objective response. At the maximum enrolment number of 54 patients, the trial was powered at 80% and based on receptors on immune effector cells, such as neutrophils, macrophages and NK cells (Clynes levels cytotoxicity and the clinical responses. This high variability in observed ADCC capacity and number of NK cells was also found in healthy donors (personal observations), suggesting that the observed variation was not the Nebivolol result of the disease status of the patients. Molecular studies have shown significant polymorphism in the genes for the different Fc receptors (Vance RIIIA expression polymorphism is probably correlated with the ability of NK cells to perform ADCC. This may be the reason that no correlation between the proportion of NK cells and the level of WX-G250-mediated ADCC was observed. Rabbit Polyclonal to PCNA In summary, the weekly schedule of intravenous WX-G250 in patients with mRCC was safe and well tolerated. The evaluation Nebivolol of the immunogenicity of WX-G250 demonstrated that an increased level of HACA does not lead to clinical symptoms. In our trial, one complete responder, one minor response and a substantial number of durable disease stabilisations were observed with WX-G250 monotherapy. The median survival after study entry was 15 months. This suggests the capacity of WX-G250 to modulate the natural history of metastatic RCC. Nebivolol Recently, it was shown that a variety of cytokines, for example, IL-2 and IFN em /em , led to the upregulation of WX-G250-mediated ADCC (Liu em et al /em , 2002). Subsequently, phase II trials optimising treatment schedules with WX-G250 by combination with cytokines have been initiated. Acknowledgments This research was sponsored by Wilex AG, Munich, Germany. Egbert Oosterwijk was supported by the Ludwig Institute for Cancer Research, New York, NY, USA..