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O C Boerman

Publications and source records attributed to O C Boerman.

126 records · Page 7Linked to original sources
PubMed1991

Novel antigens characteristic of neuroendocrine malignancies.

The authors describe the immunochemical detection, biochemical characterization, and tissue distribution of neuroendocrine antigens recognized by three newly developed monoclonal antibodies (MoAb) obtained after immunization of mice with the variant small cell lung cancer (SCLC) cell line NCI-H82. RNL-1 was reactive with neuroendocrine tissues similar to the SCLC cluster-1 MoAb, known to recognize N-CAM. Antibodies RNL-2 and RNL-3 are directed against different epitopes on the same proteinaceous complex. Both MoAb recognize an intracellularly located, water-soluble antigen which has a subunit composition with a protein triplet ranging in molecular weight between 44 and 45 kilodaltons (kD) next to a component of approximately 30 kD. The antibodies RNL-2 and RNL-3 reacted with a subset of neuroendocrine tissues and neuroendocrine neoplasms. In lung cancer both antibodies reacted only with some SCLC and carcinoids and not with nonneuroendocrine lung carcinomas. The potential diagnostic applicability of antibodies RNL-1, RNL-2, and RNL-3 is discussed.

Animals↗
PubMed1991

The effect of antibody protein dose on the uniformity of tumor distribution of radioantibodies: an autoradiographic study.

The inaccessibility of radiolabeled antibody to poorly vascularized regions of solid tumors may reduce the therapeutic efficacy of these macromolecules. Theoretical mathematical models have predicted that increasing the protein dose administered would reduce the heterogeneity of radioantibody distribution. This investigation was undertaken to evaluate this hypothesis in experimental animal models. We have utilized the technique of macroautoradiography to demonstrate an increase in tumor penetration of the lower-affinity 125I-labeled NP-4 or higher-affinity Immu-14 anti-carcinoembryonic antigen (anti-CEA) mAbs into small (60.25-0.4 g) and large (0.8-1.5 g) GW-39 and LS174T human colonic xenografts, grown subcutaneously in the nude mouse, when 400 micrograms unlabeled antibody is administered simultaneously with 10 micrograms (100 microCi) radioantibody. Further increases in protein to 800 micrograms result in a reduction in total tumor uptake of the antibody. These in a reduction in total tumor uptake of the antibody. These differences in mAb distribution could be visualized as early as 1 day after antibody injection. Improved mAb penetration was also achieved for the Mu-9 anti-CSAp (anti-mucin) antibody using 800 micrograms unlabeled antibody. An irrelevant antibody (AFP-7-31) was found to be homogeneously distributed 3 days after injection, even at a low protein dose. Attempts to improve mAb penetration by increasing the protein dose in the GS-2 colorectal tumor, a model that has low NP-4 accretion as a result physiological barriers separating antibody from antigen, were not successful. These results suggest that a more homogeneous distribution of radioantibody can be achieved by carefully selecting a dose of unlabeled antibody to coadminister. Work is currently in progress to determine the effect of improved tumor distribution of radioantibody on the therapeutic potential of a single dose of radioantibody.

Adenocarcinoma↗
PubMed1991

Comparative immunohistochemical study of four monoclonal antibodies directed against ovarian carcinoma-associated antigens.

The monoclonal antibodies OC 125, OV-TL 3, MOv 18, and OV-TL 23, which are directed against distinct ovarian carcinoma-associated antigens, are assessed in the present study for their diagnostic value. The expression of the antigens defined by these was studied in serial sections from 80 ovarian carcinomas and 103 nonovarian carcinomas obtained from 183 patients, using the immunoperoxidase technique. Immunoelectron microscopy demonstrated that the antigens were all localized on the tumor cell membrane. OC 125, OV-TL 3, and MOv 18 reacted positively with approximately 90% of the ovarian carcinoma samples (n = 80), whereas OV-TL 23 stained 76% of these samples. OC 125, OV-TL 3, and MOv 18 were also reactive with a majority of carcinomas derived from the cervix, endometrium and fallopian tube, while OV-TL 23 reactivity was primarily restricted to ovarian carcinomas. OC 125 and OV-TL 3 reacted respectively with 11% and 14% of the nongynecologic carcinomas tested (n = 64). Positive cases included breast, colon, and lung carcinomas. The antibodies MOv 18 and OV-TL 23 were found less reactive with nongynecologic carcinomas.

Antibodies, Monoclonal↗
PubMed1991

Kinetics and biodistribution in relation to tumour detection with 111In-labelled OV-TL 3 F(ab')2 in patients with ovarian cancer.

The biological behaviour of 111In-labelled OV-TL 3 F(ab')2 was studied in 22 patients with suspected ovarian cancer. After i.v. injection with 140 MBq 111In-OV-TL 3 F(ab')2 (1 mg) blood samples were taken up to 96 h and urine and faeces were collected throughout the whole study. At surgery, 5 to 7 days post-injection, primary and metastatic tumour tissues, as well as fragments of several normal tissues, were removed and 111In uptake was measured. Blood activity disappeared with half-life values of 6.1 +/- 1.1 and 17.9 +/- 6.5 h. Within 96 h excretion in urine and faeces was 16.1 +/- 2.0% i.d. (mean +/- S.D.) and 3.1 +/- 1.9% i.d., respectively. Mean tissue uptake, expressed as % i.d. kg-1 was 3.9 +/- 1.0 for primary tumour, 11.5 +/- 5.0 for liver and 0.4 +/- 0.1 for several normal background tissues. Higher tumour uptake correlated with a higher detection rate at immunoscintigraphy. However, no strict correlation was found between the amount of tumour uptake and the expression of the monoclonal antibody defined OA3 antigen. Quantitation of organ activity, using region of interest analysis, resulted in mean peak organ activities for the liver of 16% i.d., spleen 9% i.d. and kidney 4% i.d. Distribution data indicate that besides specific antibody-antigen interaction several other mechanisms play a role in uptake in tumour and other tissues.

Animals↗
PubMed1991

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

A mouse monoclonal antibody (RNL-1) was raised against the variant small cell lung cancer (SCLC) cell line NCI-H82. Immunohistochemical studies on frozen sections showed that the antibody was reactive with most SCLC (15 out of 16) and lung carcinoids (six out of seven), while in general adenocarcinomas and squamous cell carcinomas of the lung were negative. Immunocytochemical studies on 29 different cell lines derived from human lung tumours confirmed the neuroendocrine-related expression of the RNL-1 defined antigenic determinant. Immunoelectron microscopy showed that RNL-1 recognises an extracellular membrane domain, concentrated at adhesion sites between adjacent cells. The tissue distribution of the RNL-1 defined antigen was mainly restricted to neural and neuroendocrine tissues. These immunohistochemical data suggest that RNL-1 is directed against a neuroendocrine-related cell adhesion molecule. Being reactive with an epitope expressed on the surface of most neuroendocrine malignant cells, RNL-1 (IgG1 isotype) is a potential vehicle for targeting SCLC in vivo. We evaluated the ability of radiolabelled RNL-1 to localise human SCLC xenografts in nude mice as a first step in determining the in vivo value for radioimmunodetection. RNL-1 was radioiodinated using the Bolton-Hunter labelling technique. Nude mice bearing NCI-H82 xenografts were injected intravenously with the radiolabelled RNL-1 preparations, and animals were dissected 4, 24, 48, 72 and 120 h post injection (p.i.) to determine the biodistribution of the radiolabel. The iodine-125 label accumulated in the tumour up to 48 h p.i. (6.5% injected dose per gram of tissue [ID g-1]), while the label content of the normal tissues decreased with time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1991

Marker profile of different phases in the transition of normal human ovarian epithelium to ovarian carcinomas.

To investigate whether early changes in the transformation of normal ovarian epithelial cells into tumor cells can be detected with monoclonal antibodies, a comparative immunohistochemical study was performed on normal human ovarian mesothelial cells, cystomas, cystadenomas, ovarian carcinomas, as well as granulosa cell tumor. Using monoclonal antibodies against different keratin subtypes, it was shown that mesothelial cells, ovarian cysts, cystadenomas, and carcinomas all reacted positively with broad-spectrum anti-keratin monoclonal antibodies (MAbs), as well as with MAbs to keratins 7, 8, 18, and 19. Keratins 4 and 13 were not found in mesothelial cells, but positive groups of cells were identified in several cystomas, adenomas, and carcinomas. While mesothelial cells did not react with the pan-epithelial marker BW495/36, invaginating metaplastic mesothelial cells, inclusion cysts, cystomas, adenomas, and carcinomas showed an increasing reactivity with BW495/36, with an increasing degree of malignancy. The reactivity of MAbs against ovarian carcinoma-associated antigens (OV-TL 3, OC 125, MOv 18, and OV-TL 10) was limited to weak staining reaction in some mesothelial cells but were found to be positive on more than 50% of the ovarian cystadenomas and more than 90% of the ovarian carcinomas. Thecal and granulosa cells of primordial, primary, and secondary follicles all reacted positively with antibodies to the broad-spectrum keratins OV-TL 12/5 and RCK 102, and to keratins 8 and 18, but not with keratins 4, 7, 13, and 19. These keratins decreased or disappeared in granulosa cells of mature follicles (Graafian follicles), whereas granulosa cell tumors did not react with anti-keratin antibodies. The reactivity of BW 495/36 was negative or limited to traces in some granulosa cells. Ovarian carcinoma-associated antigens were not expressed in granulosa cells or granulosa cell tumors. The data indicate that mesothelial cells undergoing metaplastic changes finally resulting in ovarian cystadenomas (and carcinomas) initiate the synthesis of a 200-kd glycoprotein recognized by MAb (BW 495/36), the production of ovarian carcinoma associated antigens, in addition to focal production of keratin 4 and/or 13, as seen in several samples. The granulosa cell tumors decrease or switch off their keratin production and remain negative for the 200-kd glycoprotein and the ovarian carcinoma-associated antigens.

Adenoma↗
PubMed1990

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

Three hybridoma cell lines producing monoclonal antibodies (MAbs) against ovarian carcinomas were obtained after immunizing mice with an undifferentiated human ovarian cystadenocarcinoma extract. The hybridoma cell supernatants were initially screened for a positive immunohistochemical reaction with ovarian carcinomas concomitant with a negative reactivity with a benign ovarian cystadenoma. The antibodies OV-TL 15 (IgM), OV-TL 30 (IgG1) and OV-TL 31 (IgM) reacted positively with 84, 84 and 74% of the ovarian carcinoma samples (n = 76) respectively. Reactivity with ovarian cysts and cystadenomas (n = 21), with non-ovarian carcinomas (n = 77) and with normal human tissue samples (n = 63) was absent or limited to weak reactivity on incidental samples. All three antibodies were shown by immunoelectron microscopy to react with surface antigens (OA 15, OA 30 and OA 31) of ovarian carcinoma cells. Cross reactivity between OV-TL 15, OV-TL 30, OV-TL 31 and OC 125 monoclonal antibodies was excluded by competitive binding assays on NIH:OVCAR-3 cells. Antigen levels (OA 15 and OA 31) in tumour extracts and cyst fluids were quantified by immunoradiometric assays and compared to the CA 125 antigen levels. High levels of CA 125, OA 15 and OA 31 were found in cyst fluids from ovarian cancers. In benign ovarian cyst fluids, however, the CA 125 content was also high while OA 15 antigen was hardly detectable. The OA 31 antigen was present at relatively low levels. The IRMA data confirmed the immunohistochemical data showing that, in contrast to OC 125, the newly developed MAbs OV-TL 15, OV-TL 30 and OV-TL 31 discriminate between benign ovarian cystadenomas and malignant ovarian cancers.

Antibodies, Monoclonal↗
PubMed1990

Heterophilic antibodies in human sera causing falsely increased results in the CA 125 immunofluorometric assay.

An in-house OC 125 monoclonal antibody-based "sandwich" immunofluorometric assay (IFMA) described previously (Clin Chem 1987; 33:2191-4) gave higher results for CA 125 in 37 of 123 serum samples than did a commercially available immunoradiometric assay (IRMA). Discordant results between the two assays became concordant when measurements of the samples were repeated with normal mouse serum (100 mL/L) included in the IFMA reagent. The murine immunoglobulins are thought to block the ability of the heterophilic antibodies in the human serum samples to cross-link the labeled antibody with the solid-phase antibody. Using an enzyme immunoassay, we demonstrated human anti-mouse antibodies (HAMA) in most of the discordant samples examined. We tested the ability of nonimmune sera from other animal species to lower the apparent CA 125 concentrations of the spurious samples and observed that rat, goat, and sheep serum were less effective than mouse serum. One serum sample was discovered to give a falsely increased CA 125 result with the IRMA, but this increase could be prevented by adding murine serum to the IRMA reagent. We conclude that falsely increased CA 125 results are best prevented by adding murine serum (or murine antibodies) to the assay buffer.

Antibodies, Heterophile↗
PubMed1989

Sensitive determination of circulating anodic antigen in Schistosoma mansoni infected individuals by an enzyme-linked immunosorbent assay using monoclonal antibodies.

From a panel of mouse monoclonal antibodies reactive with a repeating epitope of the schistosome circulating anodic antigen, an IgG1 monoclonal antibody was selected. This monoclonal antibody was applied in a sandwich enzyme-linked immunosorbent assay as capture antibody and as alkaline phosphatase labeled conjugate. This assay allowed a sensitive quantitation of circulating anodic antigen in serum samples of infected individuals, detecting less than 1 ng antigen/ml serum. In Schistosoma mansoni infected individuals from Zaire, the level of antigen in serum correlated with fecal egg output. The lower detection level of the immunoassay corresponded to a level of about 10 eggs/gm feces.

Animals↗
PubMed1987

Time-resolved immunofluorometric assay for the ovarian carcinoma-associated antigenic determinant CA 125 in serum.

A time-resolved immunofluorometric assay (IFMA) is described for quantifying the ovarian carcinoma-associated antigenic determinant CA 125 in human serum. Monoclonal antibody to CA 125 is immobilized onto a microtiter well, and the same antibody labeled with a europium chelate is used as a tracer. After the immunoreaction the bound portion of the labeled antibody is quantified by dissociating the Eu3+ in a fluorescence-enhancement solution and measuring its fluorescence with a time-resolved fluorometer. The detection limit of the IFMA is 1.5 arb. units/mL, being about the same as that of a commercially available immunoradiometric assay (IRMA) for CA 125 (1.4 arb. units/mL). The analytical range of the IFMA extends to 2000 arb. units/mL, whereas the range of the IRMA is 500 arb. units/mL. For 29 serum samples from ovarian-cancer patients measured simultaneously in the IFMA and IRMA, orthogonal regression analysis gave the equation CA 125 (IFMA) = 0.9937 CA 125 (IRMA) - 1.211 arb. units/mL (Syx = 6.8681, r = 0.9932). Apparently, the IFMA for CA 125 is a convenient alternative to the IRMA for CA 125 because of short counting times, the use of nonradioactive, stable reagents, and the much-extended measuring range. Additionally, the microtiter format should lend itself to more fully automated procedures in laboratories doing many such analyses.

Antigens, Neoplasm↗
PubMed1982

Primary gene products of bovine beta-crystallin and reassociation behavior of its aggregates.

beta-Crystallin from calf lens cortex was fractionated in three different aggregates of increasing size: beta L2- beta L1 and beta H. of which the subunit composition was revealed by 2-dimensional gel electrophoresis. While beta L2 mainly consists of beta Bp (the major polypeptide chain in all three aggregates). beta L1 is characterized by the addition of a neutral and two acidic chains, and beta H contains moreover two basic chains. Translation of calf lens polyribosomes in a reticulocyte cell-free system allowed the identification of six beta-crystallin subunits as primary gene products. The distribution of these newly synthesized polypeptides over the three aggregates was established after gel filtration in the presence of carrier lens proteins. The aggregation behavior of the beta-crystallin chains was studied by dissociation reassociation experiments. The three separate aggregates could be reversibly dissociated. Reassociation of basic, neutral and acidic polypeptides, isolated by ion-exchange chromatography of beta-crystallin, produced a beta H-like aggregate. The neutral and acidic polypeptides reassociated into a beta L1-like aggregate, while the neutral polypeptides gave dimers like beta L2. A beta H-like aggregate could also be obtained by reaggregation of beta L2 with the acidic and basic chains of beta H. On the basis of these results a preliminary model for the formation of beta-crystallin aggregates is discussed.

Animals↗
PubMedDate not supplied

Time-resolved immunofluorometric assay (TR-IFMA) for the detection of the schistosome circulating anodic antigen.

We report the development of a time-resolved immunofluorometric assay (TR-IFMA) for the quantitative determination of the schistosome circulating anodic antigen (CAA). A mouse monoclonal antibody (line 120-1B10-A), recognizing a repetitive epitope on CAA, was used as both antigen-capture antibody and as Europium-labelled antigen-detecting antibody. The lower detection limit of the assay was 20 pg of trichloroacetic acid soluble fraction of adult worm antigen (AWA-TCA) per ml, with a nearly linear measuring range from 20 pg to 130 ng AWA-TCA per ml. The TR-IFMA was compared with an enzyme-linked immunosorbent assay (ELISA), in which the same monoclonal antibody was used as antigen-capture antibody and as alkaline phosphatase-conjugated antibody. The lower detection limit of the TR-IFMA was tenfold lower than that of the ELISA, while the linear range of the TR-IFMA exceeded that of the ELISA one hundred-fold. Serum samples of 80 Burundese individuals infected with Schistosoma mansoni (egg counts ranging from 4 to 2583 eggs per gram of faeces) were tested in both assays. Antigen concentrations in serum of individuals infected with S. mansoni ranged from 0-500 ng AWA-TCA per ml. The correlation between antigen levels measured by TR-IFMA and ELISA was good: Spearman's p = 0.92. Whereas in the ELISA the samples had to be titrated, the wide linear range of the TR-IFMA allowed the assay to be performed at a single serum dilution, at which an exact estimation of the antigen concentration was possible.

Adolescent↗
PubMedDate not supplied

Intraperitoneal radioimmunotherapy in an ovarian carcinoma mouse model: Effect of the radionuclide.

Despite debulking surgery and multidrug chemotherapy, advanced stage ovarian cancer has a high mortality rate. Radioimmunotherapy (RIT) is a treatment modality using specific, radiolabeled antibodies that guide cytotoxic radionuclides to cancer cells. In the present study, the therapeutic efficacy of RIT with murine monoclonal antibody HMFG1 labeled with three different beta-radiation emitting radionuclides (90Yttrium, 186Rhenium, and 131Iodine) was assessed in athymic BALB/c mice with intraperitoneally growing NIH:OVCAR-3 ovarian carcinoma xenografts. Each of the three intraperitoneally administered radiolabeled antibody preparations (90Y-HMFG1, 186Re-HMFG1, and 131I-HMFG1) caused a significant delay in ascites formation and mortality as compared to the control groups treated with 90Y-labeled irrelevant antibody, nonradiolabeled HMFG1, or phosphate buffered saline. Intraperitoneally (ip) administered 90Y-HMFG1 was shown to have a significantly higher abdominal retention as compared to the intraperitoneally administered irrelevant antibody 90Y-G250. Furthermore, intraperitoneally administered 90Y-HMFG1 more effectively inhibited tumor growth than intravenously administered 90Y-HMFG1. It was concluded that in intraperitoneally located malignant disease with ascitic cell clusters and tumor deposits, intraperitoneal administration of RIT seemed preferable as compared to intravenous administration. The choice of the most optimal radionuclide in intraperitoneally located malignancies needs further research, but could well depend on tumor characteristics such as the size of the tumor lesions.

Animals↗
PubMedDate not supplied

Immunohistochemical analysis of tumor antigen saturation following injection of monoclonal antibody G250.

Clinical tumor targeting studies with monoclonal antibody (mAb) G250 showed excellent targeting of primary renal cell carcinomas (RCC). However, tumor uptake decreased at higher mAb G250 doses, suggesting saturation of the G250 antigenic determinants. In this immunohistochemical study we investigated the saturability of G250 antigen sites after i.v. administration of mAb G250 at various protein doses in nude mice with RCC xenografts. Five groups of mice received five different protein doses (1, 3, 10, 30 or 100 micrograms) of murine mAb G250. Three days post injection mice were killed and the tumors were removed. Free G250 antigen sites, i.e., not targeted by the i.v. injected murine mAb G250 were determined by immunohistochemical staining with chimeric mAb G250. Distinct staining of the G250 antigen was observed only at the 1 and 3 micrograms dose whereas G250 antigen staining at higher doses was virtually negative. The results of this study indicate that saturation of antigen occurs at relatively low doses of i.v. administered mAb G250. Apparently, all antigenic determinants present on the RCC tumor cells were targeted, while previous preclinical studies suggested that i.v. administration of mAb G250 only saturated the accessible antigen sites.

Animals↗
PubMedDate not supplied

Biodistribution of iodine-125 and indium-111 labeled OV-TL 3 intact antibodies and F(ab')2 fragments in tumor-bearing athymic mice.

The monoclonal antibody OV-TL 3, directed against an ovarian carcinoma-associated antigenic determinant, was tested as a vehicle for radioimmunolocalization of ovarian carcinomas in athymic mice bearing NIH:OVCAR-3 xenografts. The biodistribution of intact. OV-TL 3 was compared with the distribution of OC 125. Tumor uptake with OV-TL 3 was significantly higher than with OC 125, and almost 7 times higher than with a non-specific control antibody (OV-TL 19). Administration of a mixture of intact OV-TL 3 and OC 125 did not improve tumor uptake in comparison with OV-TL 3 alone. Subsequently, intact OV-TL 3 and its F(ab')2 fragments were labeled with either 111In or 125I. The highest tumor uptake was obtained with 111In-labeled intact OV-TL 3 (14.7% ID/g, 48 hr p.i.). For both antibody forms uptake of 111In in liver, spleen and kidneys was very high. Furthermore, 111In cleared more slowly from most tissues than 125I. As a result, tumor/tissue ratios with 111In-labeled OV-TL 3 were lower than with 125I-labeled OV-TL 3. The highest tumor/tissue ratios (6.9 to 53) were obtained with 125I-labeled OV-TL 3 F(ab')2 fragments, 48 hr post injection. 111In-labeled OV-TL 3 F(ab')2 has already been shown to be a clinically useful label for the detection of ovarian cancer. The results of our comparative animal study suggest that these clinical results may even be improved by using 123I-labeled OV-TL 3 F(ab')2.

Animals↗
PubMedDate not supplied

Immunocytochemical detection of ovarian carcinoma cells in serous effusions.

Monoclonal antibodies OC 125, OV632, OV-TL 3, MOv18 and OV-TL 23, directed against distinct ovarian carcinoma-associated antigens, were examined for their value in cytopathologic diagnosis. Their sensitivity and specificity in staining ovarian carcinoma cells in serous effusions we determined using the indirect immunoperoxidase technique. Smears prepared from 140 serous effusions (73 benign, 67 malignant) were immunostained with the five antibodies. OC 125 and MOv18 reacted positively with 96% and 81% of the smears of effusions from ovarian carcinoma patients, respectively, while OV-TL 3, OV632 and OV-TL 23 stained a lower percentage of the samples (73%, 65% and 62%, respectively). In discriminating ovarian carcinoma cells from benign (mesothelial or inflammatory) cells in serous effusions, MOv18 demonstrated the highest specificity (100%) since none of the 73 samples from benign effusions were stained upon incubation with this antibody. OC 125 cannot be used for this purpose due to its reactivity with mesothelial cells in benign samples. Staining cytologic preparations of malignant effusions from cancer patients with carcinomas not originating in the ovary revealed that OV632 and OV-TL 23 may be useful adjuncts to determine the origin of the carcinoma cells found in serous effusions. The reactivity of these antibodies was highly selective for ovarian carcinoma cells, staining only 6% and 0% of the samples from the non-ovarian carcinoma samples, respectively. It is concluded that MOv18 is the most suitable antibody for distinguishing ovarian carcinoma cells from mesothelial cells in serous effusions, while OV632 and OV-TL 23 especially may help to assess whether carcinoma cells found in effusions originate in the ovary.

Antibodies, Monoclonal↗
PubMedDate not supplied

Tumour targeting of the anti-ovarian carcinoma x anti-CD3/TCR bispesific monoclonal antibody OC/TR and its parental MOv18 antibody in experimental ovarian cancer.

The anti-tumour x anti-T-cell bispecific monoclonal antibody (biMAb) OC/TR is a biologically produced biMAb combining the anti-ovarian carcinoma activity of the MOv18 MAb with anti-CD3/T-cell receptor (TCR) complex activity. In this study, the in vitro binding characteristics of the OC/TR biMAb and its tumour targeting potential in nude mice with Hela tumours was studied. Scatchard analysis revealed that the affinity constant of the biMAb was 7 times lower than the affinity of the parental MOv18 antibody. Uptake of the OC/TR antibody in the Hela xenografts in nude mice was significantly higher than the tumour uptake of an irrelevant control antibody, indicating that the radioiodinated OC/TR biMAb specifically localized in the tumour xenografts. However, tumour uptake was significantly lower than the tumour uptake of the parental MOv18 antibody. This reduced tumour uptake most likely is a result of its reduced affinity. We conclude that, despite the loss of bivalent tumour cell binding, the biMAb OC/TR can still specifically localize in tumours. This indicates that the first prerequisite of an effective therapeutic approach using systemically applied biMAb can be met. Whether the interaction with human T-cells will affect the tumour targeting potential of the biMAb in patients remains to be investigated.

Animals↗