title: A pilot study of monoclonal antibody cG250 and low dose subcutaneous IL-2 in patients with advanced renal cell carcinoma.
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/m(2)/week, first and fifth doses trace-labelled with (131)I), and 1.25 x 10(6) IU/m(2)/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. (131)I-labeled cG250 showed excellent targeting of tumour deposits. (131)I cG250 PK: T(1/2)alpha 20.16 +/- 6.59 h, T(1/2)beta 126.21 +/- 34.04 h, CL 39.67 +/- 23.06 mL/h, Cmax 5.12 +/- 0.86 microg/mL, V(1) 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.
authors: Ludwig Institute for Cancer Research, Victoria, Australia. Ian.Davis@ludwig.edu.au
authors: Ian D
authors: ID
authors: Davis
authors: Zhanqi
authors: Z
authors: Liu
authors: Wayne
authors: W
authors: Saunders
authors: Fook-Thean
authors: FT
authors: Lee
authors: Violeta
authors: V
authors: Spirkoska
authors: Wendie
authors: W
authors: Hopkins
authors: Fiona E
authors: FE
authors: Smyth
authors: Geoffrey
authors: G
authors: Chong
authors: Anthony T
authors: AT
authors: Papenfuss
authors: Bridget
authors: B
authors: Chappell
authors: Aurora
authors: A
authors: Poon
authors: Timothy H
authors: TH
authors: Saunder
authors: Eric W
authors: EW
authors: Hoffman
authors: Lloyd J
authors: LJ
authors: Old
authors: Andrew M
authors: AM
authors: Scott
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D000951:Antigens, Neoplasm / Q000276:immunology*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000276:immunology*; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000276:immunology* / Q000628:therapy*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011877:Radionuclide Imaging
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; C106533:G250 monoclonal antibody; D007376:Interleukin-2; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
references: J Urol. 2004 Jun;171(6 Pt 1):2461-6
references: 15126876
references: J Nucl Med. 2004 Aug;45(8):1412-21
references: 15299069
references: Int J Cancer. 1986 Oct 15;38(4):489-94
references: 2428759
references: J Clin Oncol. 1993 Apr;11(4):738-50
references: 8478666
references: Int J Cancer. 1994 Feb 15;56(4):609-14
references: 7509324
references: Biometrics. 1996 Sep;52(3):992-1001
references: 8805764
references: J Immunother Emphasis Tumor Immunol. 1996 May;19(3):184-91
references: 8811493
references: J Clin Oncol. 1997 Apr;15(4):1529-37
references: 9193349
references: Cancer Immunol Immunother. 1998 Aug;46(6):318-26
references: 9756416
references: Clin Cancer Res. 1996 Apr;2(4):669-77
references: 9816217
references: Clin Cancer Res. 1998 Nov;4(11):2729-39
references: 9829736
references: J Clin Oncol. 2005 Jan 1;23(1):133-41
references: 15625368
references: Cochrane Database Syst Rev. 2005;(1):CD001425
references: 15674877
references: Clin Cancer Res. 2005 May 15;11(10):3714-21
references: 15897568
references: J Clin Oncol. 2005 Sep 20;23(27):6540-8
references: 16170161
references: Clin Cancer Res. 2005 Oct 1;11(19 Pt 2):7178s-7186s
references: 16203819
references: Biomarkers. 2005 Nov;10 Suppl 1:S83-6
references: 16298916
references: J Urol. 2006 Jan;175(1):57-62
references: 16406869
references: Cancer Biother Radiopharm. 2006 Jun;21(3):263-8
references: 16918303
references: N Engl J Med. 2007 Jan 11;356(2):115-24
references: 17215529
references: N Engl J Med. 2007 Jan 11;356(2):125-34
references: 17215530
references: CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66
references: 17237035
references: Lancet Oncol. 2007 Apr;8(4):304-10
references: 17395103
references: N Engl J Med. 2007 May 31;356(22):2271-81
references: 17538086
references: Cancer Immun. 2007;7:13
references: 17705349
references: Clin Cancer Res. 1999 Oct;5(10 Suppl):3268s-3274s
references: 10541374
references: J Clin Oncol. 1999 Aug;17(8):2530-40
references: 10561319
references: J Clin Oncol. 1999 Sep;17(9):2859-67
references: 10561363
references: Br J Cancer. 1999 Oct;81(4):741-6
references: 10574265
references: J Urol. 2000 Feb;163(2):408-17
references: 10647643
references: J Urol. 2000 Apr;163(4):1090-5; quiz 1295
references: 10737472
references: Cancer Immunol Immunother. 2002 May;51(3):171-7
references: 11941456
references: Clin Cancer Res. 2003 Feb;9(2):802-11
references: 12576453
references: Folia Biol (Praha). 2003;49(2):74-7
references: 12779016
references: Urol Clin North Am. 2003 Aug;30(3):623-31
references: 12953760
references: Br J Cancer. 2004 Mar 8;90(5):985-90
references: 14997194