Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/9398
Title: Anti-renal cell carcinoma chimeric antibody G250: cytokine enhancement of in vitro antibody-dependent cellular cytotoxicity.
Authors: Liu, Zhanqi;Smyth, Fiona E;Renner, Christoph;Lee, Fook-Thean;Oosterwijk, Egbert;Scott, Andrew M
Affiliation: Tumour Targeting Program, Ludwig Institute for Cancer Research, Melbourne Branch, Austin and Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia.
Issue Date: 1-Mar-2002
Citation: Cancer Immunology, Immunotherapy : Cii 2002; 51(3): 171-7
Abstract: The chimeric monoclonal antibody cG250 targets the G250 antigen, a transmembrane protein which is expressed on renal carcinoma cells and is identical to the MN/CAIX antigen. In vitro studies have previously demonstrated that cG250 induces antibody-dependent cellular cytotoxicity (ADCC) of G250-positive targets. In order to investigate the upregulation of ADCC mediated by cG250, ADCC was examined using effector cells cultured in the presence or absence of the cytokines interferon-gamma (IFN-gamma), interferon-alpha isoforms IFN-alpha (2a) and IFN-alpha (2b) and interleukin-2 (IL-2), and the time course of effects over a 7-day period was determined. Renal cell carcinoma lines expressing high (SK-RC-52) and low (SK-RC-09) G250 antigen levels were used as target cells, and freshly isolated peripheral blood mononuclear cells (PBMC) from a healthy donor were used as the effector cells. PBMC were incubated with the respective cytokine at a range of concentrations or with a media alone control for a period of 7 days. The ADCC activity mediated by cG250 or control isotype matched huA33 with the different PBMC treatment groups was assessed in triplicate daily. Corresponding lymphokine activated killing (LAK) activity was measured concurrently for each treatment group. Chimeric G250 specifically recognised G250 antigen on high and low expressing cell lines SK-RC-52 and SK-RC-09, and mediated specific in vitro ADCC of both lines. In the absence of cytokine stimulation, the specific ADCC of cG250 declined rapidly within three days. IL-2 strongly enhanced and maintained cG250-mediated ADCC activity and K562 cytotoxicity when applied to PBMC in culture for seven days. IFN-gamma also enhanced the ADCC of cG250 throughout the study period, but was not as effective as the IL-2 treatment, and the SK-RC-09 line displayed lower specific cytotoxicity than the SK-RC-52 cell line. In contrast, IFN-alpha 2a and 2b increased cG250-mediated ADCC and K562 cytotoxicity for only three days of the study period. The potent and sustained immune effector activity observed with cG250 and cytokines in this in vitro study suggests that the combination immunotherapy of cG250 with cytokines such as IL-2 shows promise in the treatment of renal cell carcinoma (RCC).
Internal ID Number: 11941456
URI: http://ahro.austin.org.au/austinjspui/handle/1/9398
DOI: 10.1007/s00262-002-0268-4
URL: http://www.ncbi.nlm.nih.gov/pubmed/11941456
Type: Journal Article
Subjects: Animals
Antibodies, Monoclonal.therapeutic use
Antineoplastic Agents.therapeutic use
Carcinoma, Renal Cell.immunology.therapy
Cell Separation
Cytokines.metabolism
Dose-Response Relationship, Drug
Flow Cytometry
Immunotherapy.methods
Interferon-gamma.metabolism
Interferons.metabolism
Interleukin-2.metabolism
Kidney Neoplasms.immunology.therapy
Killer Cells, Natural.metabolism
Mice
Time Factors
Tumor Cells, Cultured
Appears in Collections:Journal articles

Files in This Item:
File SizeFormat 
11941456.pdf46.36 kBAdobe PDFView/Open


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.