Identification of glioma-associated antigen MUC 2-63 as CD44

Abstract

SmryMonoclonal antibody MUC 2-63 recognses neuroenic tumours and has been used successfilly for radiimaging human malignant ghomas. We now show that the MUC 2-63 antigen has the same tissue distibution and molecular weght rae as the CD44 antigen and confirm the identity of these two molecule in bcking studies using MUC 2-63 and the CD44 anti-framework antibody FIO44-2. Thus not only MUC 2-63 but also other anti-CD44 monodcnal antibodies should prove useful in imaging and, perhaps, therapy of brain tumours.The CD44 molecule was orginally defined by the monoclonal antibody FIO 442 and found predominantly on lymphohaemopoietic tissues and brain (Dalhau et al., 1980, Stoll et al., 1989 al., 1989;Stamenkovic et al., 1989). It is acquired by medullary thymocytes during T-cell maturation in the thymus and is up-regulated on memory T cells (Dalchau et al., 1980;Haynes et al., 1983; Sanders et al., 1988). CD44 is also present at low levels on normal epithelium, but is highly expressed on carcnomas, including those of the colon (Daar & Fabre, 1983; Stamenovic et al., 1989). In human brain the molecule has a molkeular weight of 90kDa, while a lymphoid form of 80-90kDa (CD44H) and an epitheial form of 160 kDa (CD44E) have been described (McKenzie et al., 1982;Stamenkovic et al., 1989 Stamenkovic et al., , 1991 Brown et al., 1991). The diferences between these and other isoforms, ranging in molcular weight from 85 to 250 kDa, lie in the membraneproximal region and result from alternative splicing of at least ten different exons and from post-translational modifications (Brown et al., 1991; Jackson et al., 1992; Screaton et al., 1992; Tolg et al., 1993).Many functions involving cell-cell and cell-extracellular matrix interactions have been attributed to CD44, and are likely to be mediated by different isoforms (Belitsos et al., 1990; Staovic et al., 1991;Jalkanen & Jalkanen, 1992). Such interactions play a role in cell development, activation and migration (Berg et al., 1989; Miyake et al., 1990; Ritter & Crispe, 1992;Haegel et al., 1994

CD44 expression in primary and recurrent oligodendrogliomas and in adjacent gliotic brain tissue

“…The slides were treated in a microwave oven (750 W) twice for 6 min in 10 mM citrate buffer (pH 6.0) for demascation of the antigen followed by incubation in 0.3% H 2 O 2 in methanol. Then, 10% goat serum was applied for 30 min followed by MUC 2‐63 antibody directed against the standard form of CD44 at a concentration of 10 μg/ml for 60 min [ 21, 22]. Biotinylated secondary antibody (1:60, goat anti‐mouse, Sigma, Poole, UK) and peroxidase‐labelled streptavidin (1:100–1:200, Dako, Hamburg, Germany) were added in sequence.…”

Neoplasia

“…Nevertheless, production of human antibodies, recombinant antigen-specific molecules like chimeric antibodies, single chain fragments of the variable region (scFv), and immunotoxins usually yield lower quantities. Various procaryontic and eucaryontic expression systems for production of fusion proteins are now available for different purposes ( 5 ) .…”

“…Since human mAbs are rare and human hybridomas are seldomly stable, one of the first antibody constructs consisted of the murine genes coding for the variable region domains combined with human constant region domain genes. The resulting chimeric mouse/human mAbs showed reduced immunogenicity and improved ADCC and CDC (5). Apossibility to further 'humanize.. mAbs consists of grafting of the framework regions.…”

“…Because Fab or scFv suffice for antigen recognition, these molecules may be applied instead of whole mAbs in immunoszintigraphy, thereby reducing immunogenicity of the molecules and improving tumor penetration and accelerating antibody clearance ( 5 ) .…”

MUC16 mutation is associated with tumor grade, clinical features, and prognosis in glioma patients

“…Some members of the mucin family have been detected in gliomas (Hagel et al 1994; Romeijn et al 1994; Oosterkamp et al 1997). However, to date, MUC16 mutations have not yet been explored in these tumors.…”