Molecular cloning and immunogenicity of renal cell carcinoma-associated antigen G250

Grabmaier, Karin; Vissers, Joost L. M.; Weijert, Mirjam C. A. de; Oosterwijk-Wakka, J.C.; Bokhoven, A. van; Brakenhoff, R.H.; Noeßner, Elfriede; Mulders, Peter; Merkx, G.F.M.; Figdor, Carl G.; Adema, Gosse J.; Oosterwijk, Egbert

doi:10.1002/(sici)1097-0215(20000315)85:6<865::aid-ijc21>3.0.co;2-q

Cited by 157 publications

(104 citation statements)

References 17 publications

Supporting

Mentioning

100

Contrasting

Unclassified

Order By: Relevance

“…Figure 4 shows that a partial shift in the FACS profile was observed for the colorectal cancer cell line LS174T, whereas a very marked increase of cell fluorescence was detected for the pVHL-defective human RCC cell line SK-RC-52, similar to what previously reported for the clinical-stage cG250 monoclonal antibody (Grabmaier et al, 2000).…”

Section: In Vitro Characterisation Of A3 and Cc7 Antibodiessupporting

confidence: 81%

Human monoclonal antibodies targeting carbonic anhydrase IX for the molecular imaging of hypoxic regions in solid tumours

et al. 2009

View full text Add to dashboard Cite

BACKGROUND: Hypoxia, which is commonly observed in areas of primary tumours and of metastases, influences response to treatment. However, its characterisation has so far mainly been restricted to the ex vivo analysis of tumour sections using monoclonal antibodies specific to carbonic anhydrase IX (CA IX) or by pimonidazole staining, after the intravenous administration of this 2-nitroimidazole compound in experimental animal models. METHODS: In this study, we describe the generation of high-affinity human monoclonal antibodies (A3 and CC7) specific to human CA IX, using phage technology. RESULTS: These antibodies were able to stain CA IX ex vivo and to target the cognate antigen in vivo. In one of the two animal models of colorectal cancer studied (LS174T), CA IX imaging closely matched pimonidazole staining, with a preferential staining of tumour areas characterised by little vascularity and low perfusion. In contrast, in a second animal model (SW1222), distinct staining patterns were observed for pimonidazole and CA IX targeting. We observed a complementary pattern of tumour regions targeted in vivo by the clinical-stage vascular-targeting antibody L19 and the anti-CA IX antibody A3, indicating that a homogenous pattern of in vivo tumour targeting could be achieved by a combination of the two antibodies. CONCLUSION: The new human anti-CA IX antibodies are expected to be non-immunogenic in patients with cancer and may serve as broadly applicable reagents for the non-invasive imaging of hypoxia and for pharmacodelivery applications.

show abstract

Section: In Vitro Characterisation Of A3 and Cc7 Antibodiessupporting

confidence: 81%

Human monoclonal antibodies targeting carbonic anhydrase IX for the molecular imaging of hypoxic regions in solid tumours

et al. 2009

View full text Add to dashboard Cite

show abstract

“…CA9 is a known antigen currently being targeted for RCC immunotherapy (Divgi et al, 1998;Steffens et al, 1999;Uemura et al, 1999;Grabmaier et al, 2000;Li et al, 2001;Bui et al, 2003;Kennett, 2003). To compare expression of CD70 with CA9, we performed real-time quantitative RT -PCR analysis on multiple normal tissues and clinical RCC samples (Figure 7).…”

Section: Cd70 Exhibits a More Restricted Normal Tissue Distribution Amentioning

confidence: 99%

“…Antibodies can also be used to specifically deliver cytotoxic drugs to tumour cells as immunoconjugates that bind to, and internalise with, highly expressed cell surface antigens. An example of an antigen found to be overexpressed in RCC is carbonic anhydrase IX (CA9), which is the target for the monoclonal antibody (mAb) G250 (Pastorek et al, 1994;Uemura et al, 1999;Grabmaier et al, 2000;Li et al, 2001;Bui et al, 2003). Immunoscintigraphy of RCC patients dosed with iodine-131-labelled G250 demonstrated tumour targeting to metastatic sites (Divgi et al, 1998;Steffens et al, 1999;Kennett, 2003).…”

mentioning

confidence: 99%

CD70 (TNFSF7) is expressed at high prevalence in renal cell carcinomas and is rapidly internalised on antibody binding

Pj¹,

Ja²,

Steers

et al. 2006

Br J Cancer

View full text Add to dashboard Cite

In order to identify potential markers of renal cancer, the plasma membrane protein content of renal cell carcinoma (RCC)-derived cell lines was annotated using a proteomics process. One unusual protein identified at high levels in A498 and 786-O cells was CD70 (TNFSF7), a type II transmembrane receptor normally expressed on a subset of B, T and NK cells, where it plays a costimulatory role in immune cell activation. Immunohistochemical analysis of CD70 expression in multiple carcinoma types demonstrated strong CD70 staining in RCC tissues. Metastatic tissues from eight of 11 patients with clear cell RCC were positive for CD70 expression. Immunocytochemical analysis demonstrated that binding of an anti-CD70 antibody to CD70 endogenously expressed on the surface of A498 and 786-O cell lines resulted in the rapid internalisation of the antibody -receptor complex. Coincubation of the internalising anti-CD70 antibody with a saporin-conjugated secondary antibody before addition to A498 cells resulted in 50% cell killing. These data indicate that CD70 represents a potential target antigen for toxin-conjugated therapeutic antibody treatment of RCC.

show abstract

“…It is interesting that another HIF target, CAIX, encodes a renal carcinoma antigen previously called G250 (10,127,128). Antibodies against G250 might be used to localize tumors and, in time, as therapeutics.…”

Section: Implications For Therapymentioning

confidence: 99%

The von Hippel-Lindau Gene, Kidney Cancer, and Oxygen Sensing

Kaelin¹

2003

Journal of the American Society of Nephrology

115

View full text Add to dashboard Cite

Abstract. Recent studies of a relatively rare hereditary cancer syndrome, von Hippel-Lindau (VHL) disease, have shed new light on the molecular pathogenesis of kidney cancer and, perhaps more important, on how mammalian cells sense and respond to changes in oxygen availability. This knowledge is already translating into new therapeutic targets for kidney cancer as well as for multiple conditions, such as myocardial infarction and stroke, in which ischemia plays a pathogenic role. This review summarizes the current knowledge of the molecular pathogenesis of von Hippel-Lindau disease and the role of the VHL gene product (pVHL) in kidney cancer and the mammalian oxygen sensing pathway.

show abstract

Molecular cloning and immunogenicity of renal cell carcinoma-associated antigen G250

Cited by 157 publications

References 17 publications

Human monoclonal antibodies targeting carbonic anhydrase IX for the molecular imaging of hypoxic regions in solid tumours

Human monoclonal antibodies targeting carbonic anhydrase IX for the molecular imaging of hypoxic regions in solid tumours

CD70 (TNFSF7) is expressed at high prevalence in renal cell carcinomas and is rapidly internalised on antibody binding

The von Hippel-Lindau Gene, Kidney Cancer, and Oxygen Sensing

Contact Info

Product

Resources

About