A pilot study of monoclonalantibody cG250 and low dose subcutaneous IL-2 in patients with advanced renalcell carcinoma

摘要

The chimeric monoclonal antibody cG250 recognizes the CAIX/MN antigen. cG250 induces antibody-dependent cellular cytotoxicity (ADCC) responses in vitro that can be enhanced by IL-2. We studied the effects of adding daily low-dose subcutaneous IL-2 to cG250 for treatment of clear cell renal cell carcinoma (RCC). The primary endpoints of the trial were toxicity and immunological effects (human anti-chimeric antibodies [HACA], ADCC, natural killer [NK] and lymphokine-activated killer cell [LAK] activity); secondary endpoints were cG250 biodistribution and pharmacokinetics (PK) and tumour response rates. Eligible patients had unresectable metastatic or locally advanced clear cell RCC with measurable or evaluable disease. Nine patients were treated with six doses of cG250 (10 mg/m²/week, first and fifth doses trace-labelled with ¹³¹I), and 1.25 x 10⁶ IU/m²/day IL-2 for six weeks. Treatment was generally well tolerated with no adverse events attributable to cG250. Two patients required a 50% dose reduction of IL-2 due to toxicity. No HACA was detected. ¹³¹I-labeledcG250 showed excellent targeting of tumour deposits. ¹³¹IcG250 PK: T½α 20.16 ± 6.59 h, T½β 126.21 ± 34.04 h, CL39.67 ± 23.06 mL/h, Cmax 5.12 ± 0.86 µg/mL,V1 3.88 ± 1.05 L. IL-2 didnot affect cG250 PK. A trend for increased percentage of circulatingCD3-/CD16+CD56+ NK cells was observed.Some patients showed enhanced ADCC or LAK activity. No antitumour responseswere observed. In conclusion, weekly cG250 with daily low-dose subcutaneousIL-2 is well tolerated. IL-2 does not influence cG250 biodistributionor increase HACA.