Article

Cancer Immunity, Vol. 7, p. 14 (17 August 2007) Submitted: 20 July 2007. Accepted: 20 July 2007.

A pilot study of monoclonal antibody cG250 and low dose subcutaneous IL-2 in patients with advanced renal cell carcinoma

Ian D. Davis1,2, Zhanqi Liu1, Wayne Saunders2, Fook-Thean Lee1, Violeta Spirkoska1, Wendie Hopkins1, Fiona E. Smyth1, Geoffrey Chong1, Anthony T. Papenfuss3, Bridget Chappell2, Aurora Poon2, Timothy H. Saunder2, Eric W. Hoffman4, Lloyd J. Old4 and Andrew M. Scott1,2

1Ludwig Institute for Cancer Research, Victoria, Australia

2Austin Hospital, Victoria, Australia

3Walter and Eliza Hall Institute of Medical Research, Victoria, Australia

4Ludwig Institute for Cancer Research, New York, NY, USA

Contributed by: LJ Old

Keywords: clinical trial, renal cell carcinoma, human CA9 protein, cG250, chimeric antibody, IL-2

Abstract

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-labeled cG250 showed excellent targeting of tumour deposits. 131I cG250 PK: T½α 20.16 ± 6.59 h, T½β 126.21 ± 34.04 h, CL 39.67 ± 23.06 mL/h, Cmax 5.12 ± 0.86 µg/mL, V1 3.88 ± 1.05 L. IL-2 did not affect cG250 PK. A trend for increased percentage of circulating CD3-/CD16+CD56+ NK cells was observed. Some patients showed enhanced ADCC or LAK activity. No antitumour responses were observed. In conclusion, weekly cG250 with daily low-dose subcutaneous IL-2 is well tolerated. IL-2 does not influence cG250 biodistribution or increase HACA.