Monoclonal antibodies that discriminate between human ovarian carcinomas and benign ovarian tumours

Boerman, Otto C.; Makkink, W.K.; Thomas, Chris M.G.; Hanselaar, A. G. J. M.; Yedema, C.A.; Kenemans, P.; Poels, L. G.

doi:10.1016/0277-5379(90)90293-3

Cited by 10 publications

(8 citation statements)

References 23 publications

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“…while 0V-TLI6 was produced independently, using a completely different procedure by immunization with cyst fiuid from a pooriy differentiated ovarian carcinoma [9]. Both antibodies are of the IgGl subtype, and have been shown to have similar binding characteristics [10]. The affinity constants of both antibodies are virtually identical (approximately l-l-l 4x 10^ M"').…”

Section: Discussionmentioning

confidence: 99%

“…The following MoAbs directed to ovarian carcinomaassociated antigens were used: OV-TL3 [2], 0V-TL16 [9]. OV-TL30 [10] and M0vl8 [12]; kindly supplied by Dr M. Colnaghi (National Cancer Institute. Milan.…”

Section: Cell Lines and Antibodiesmentioning

confidence: 99%

“…The immunohistochemical reactivity patterns of 0V-TLI6 and OV-TL3 with ovarian carcinomas and some other (neoplastic) tissues are similar [4]. Tumour uptake and biodistdbution patterns in nude mice bearing ovarian cancer xenografts as well as binding affinity, binding characteristics and the number of antigenic determinants per ceil, were identical for both antibodies [10]. These data suggest that both antibodies, although obtained by completely different immunization protocols and with a time interval of 2 years, might recognize an identical antigen or even the same epitope on ovarian carcinoma cells.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of idiotope structure of ovarian cancer antibodies: recognition of the same epitope by two monoclonal antibodies differing mainly in their heavy chain variable sequences

Slobbe

Poels

Dam

et al. 1994

Clinical and Experimental Immunology

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SUMMARYTwo MoAbs, independently raised against ovarian carcinoma cells and referred to as 0V-TL3 and 0V-TL16, display an identical reaction pattern with a membrane-associated protein in both normal and malignant ovarian cells. Also, a similar binding affinity constant and a similar number of binding sites per cell indicate that both MoAbs bind to the same antigen. Competition assays reveal that OV-TLI6 is able to compete with 0V-TL3 for binding to OVCAR-3 cells. Epitope mapping using a filamentous phage hexapeptide epitope library showed that both MoAbs are able to select identical phages, suggesting that their epitopes are identical or at least overlapping. However, purified polyclonal and monoclonal anli-idiotypic antibodies directed against 0V-TL3 failed lo recognize the 0V-TL16 idiotype, indicating that the .structure of the antigen-binding regions of both antibodies is distinct. This was corroborated by molecular cloning and sequencing of the variable heavy (VH) and light (VJ chain immunogiobulin regions of both MoAbs. The Vr egions of both antibodies were found to be distinct, whereas the VL regions are almost identical. Computer modelling of the idiotypes suggests that the complementarity determining regions (CDR). with the exception of VHCDR3, have (almost) identical spatial configurations. Our data indicate that, although structurally different in their VH regions, OV-TL3 and OV-TL16 are able to bind to identical epitopic regions on the antigen, because differences in primary structure do not exclude the formation of sufficient and similar spatial structures for the interaction with an epitope.Keywords immunogiobulin variable domains ovarian carcinoma phage display epitope library antibody modelling INTRODUCTIONFor the management of cancer, MoAbs raised against tumourspecific determinants have proven to be of great help. For ovarian carcinomas MoAbs have been generated, among which are 0V-TL3 and 0V-TL16, that have been raised by different immunization procedures. Both react with a membrane antigen (OA3) [1] expressed in about 90% of the ovarian tumours and only weakly expressed in normal tissue [2]. 0V-TL3, raised after immunization with an extract of an endomctrioid cancer biopsy, has a reactivity pattem highly restricted to ovarian carcinomas [3,4], and was recently shown to react with a surface Correspondence: G.J

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Section: Discussionmentioning

confidence: 99%

Section: Cell Lines and Antibodiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Analysis of idiotope structure of ovarian cancer antibodies: recognition of the same epitope by two monoclonal antibodies differing mainly in their heavy chain variable sequences

Slobbe

Poels

Dam

et al. 1994

Clinical and Experimental Immunology

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“…Immunoreactivity of the labelled antibody preparations was checked in a competitive binding assay as described earlier (Boerman et al, 1990), using NCI-H82 coated 96-well plates as the solid phase.…”

Section: Methodsmentioning

confidence: 99%

Immunotargeting of human small cell lung cancer xenografts in athymic mice using a monoclonal antibody (RNL-1) against a neuroendocrine-related antigen

Mijnheere

Boerman²,

Broers³

et al. 1991

Lung Cancer

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“…Monoclonal antibodies (MAb) to ovarian tumor-associated antigens have been devel oped by several investigators [1][2][3][4][5][6][7][8][9][10] and they have been used for several purposes. The ma jority of these tumor-associated antigens are not truly specific for tumors, as they are also expressed in normal and cancer cells of var ious origins.…”

Section: Introductionmentioning

confidence: 99%

Ovarian Carcinomas Express a Sperm Acrosomal Antigen, Defined by Monoclonal Antibody 9H8

Sikut

Veromann²,

Piirsoo³

et al. 1992

Tumor Biol

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A new monoclonal antibody (MAb 9H8, IgM class) reactive with human ovarian carcinoma has been raised after immunizing C57BL/6 mice with bovine sperm. Immunohistological studies indicated that 20/21 serous ovarian adenocarcinomas expressed 9H8-defined antigen but it was absent in benign ovarian tumors (0/11). 1/11 of breast carcinomas and 5/5 of rectal carcinomas expressed this antigen, although to a considerably lesser degree. Tumors of lung, skin, brain and mesothelium were negative. The antigen was also expressed in embryonic skin, in renal collecting tubule cells and in saliva. In bovine, human and mouse sperm the antigen is confined to the acrosomal region. The molecular weight of this antigen was determined by Western blot analysis and gel filtration. In SDS-PAGE the antigen ran as a broad band barely entering the 7% gel, indicating an apparent molecular weight > 300 kDa. In the absence of detergents and reducing agents this glycoprotein forms larger complexes ( > 1,500 kDa) as determined by gel filtration on Sephacryl S300. The epitope contains carbohydrate structures recognized by lectin PNA (peanut agglutinin).

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Monoclonal antibodies that discriminate between human ovarian carcinomas and benign ovarian tumours

Cited by 10 publications

References 23 publications

Analysis of idiotope structure of ovarian cancer antibodies: recognition of the same epitope by two monoclonal antibodies differing mainly in their heavy chain variable sequences

Analysis of idiotope structure of ovarian cancer antibodies: recognition of the same epitope by two monoclonal antibodies differing mainly in their heavy chain variable sequences

Immunotargeting of human small cell lung cancer xenografts in athymic mice using a monoclonal antibody (RNL-1) against a neuroendocrine-related antigen

Ovarian Carcinomas Express a Sperm Acrosomal Antigen, Defined by Monoclonal Antibody 9H8

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