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E Oosterwijk

Publications and source records attributed to E Oosterwijk.

At least 55 records · Page 3Linked to original sources
PubMed1995

Development and characterization of anti-renal cell carcinoma x antichelate bispecific monoclonal antibodies for two-phase targeting of renal cell carcinoma.

To test a two-step approach for radioimmunotargeting of renal cell cancer, quadroma cells secreting antichelate x anti-renal cell carcinoma bispecific antibodies were obtained by somatic cell fusion. Five monoclonal antibodies against the chelate 1,4,7-triazaheptane-N,N',N"-pentaacetic acid (DTPA) were produced and characterized. Competitive binding assays indicated that the anti-DTPA antibodies reacted with DTPA chelated with indium, yttrium, chromium, iron, or zinc. The affinity constants of the anti-DTPA antibodies for 111In-DTPA ranged from 0.19 to 0.23 nM-1. Using different chelates, a remarkable chelate specificity of the anti-DTPA antibodies was demonstrated. The chelates recognized by the antibodies DTIn1, DTIn2, and DTIn4 share a N(N")-diacetic acid group, whereas the chelates recognized by DTIn3 share a N'-acetic acid group, suggesting the presence of different essential structures within the DTPA molecule that determine the reactivity of the antibodies. Five anti-DTPA antibody-producing hybridomas were used for somatic cell fusion with hybridoma G250 directed against renal cell carcinoma, resulting in three bispecific antibody-producing quadroma cell lines. The bispecific monoclonal antibodies were purified from ascites fluid using protein A affinity chromatography followed by hydroxylapatite chromatography and/or cation exchange chromatography. Of the total IgG amount present in the ascites fluid, 10-15% represented the bispecific antibodies. These bispecific antibodies will allow testing and optimization of a two-step approach for radioimmunotargeting of chelated radionuclides.

Animals↗
PubMed1995

Radiolabeled monoclonal antibody G250 in renal-cell carcinoma.

The current status of iodine 131-radiolabeled monoclonal antibody G250 (mAb G250) in renal-cell carcinoma (RCC) is described. This mAb recognizes a tumor-associated antigen that is expressed on the cell surface of almost all RCC but is not expressed on normal tissues, with the exception of gastric mucosa and larger bile ducts. On the basis of these favorable characteristics, this mAb seemed a prime candidate for clinical investigations. Preclinical animal studies and ex vivo perfusion experiments in tumor-bearing kidneys showed excellent targeting of mAb G250 to RCC tumors. Supported by these investigations, a phase I study was initiated to define the imaging and biodistribution characteristics of 131I-labeled mAb G250 in RCC patients. Specific localized of [131I]-mAb G250 to G250-antigen-positive primary and metastatic RCC was observed. In several patients, [131I]-mAb G250 imaging revealed thus far unrecognized, i.e., occult, disease. Values obtained for [131I]-mAb G250 uptake, relative as well as absolute, were among the highest reported for tumor biopsies obtained 8 days after intravenous mAb administration. The specific localization and high accumulation encouraged us to begin a phase I/II radiotherapy trial with [131I]-mAb G250. The maximal tolerable dose was reached at 90 mCi/m2 [131I]-mAb G250. In the subsequent phase I/II radiotherapy study, we observed stable disease in a great number of patients as well as minor responses in a small number of patients. Multiple treatments seemed necessary to achieve better response rates. However, anti-mouse responses prevented multiple dosing with the murine mAb G250.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Immunization with anti-idiotype monoclonal antibodies bearing the internal image of the renal-cell carcinoma-associated antigen G250 induces specific cellular immune responses.

We have previously isolated and characterized 6 anti-idiotype antibodies (Ab2s) directed against monoclonal antibody G250 (MAbG250) which reacts with a tumor-associated antigen (TAA) expressed in a large proportion of human renal-cell carcinomas (RCC). These 6 Ab2s (NUH31, 51, 71, 82, 91: IgG1, NUH44: IgG2a) showed MAbG250 binding site specificity and induction of anti-TAA antibody resembling MAbG250 (so-called AbI') in rabbits, indicating that they are internal image antibodies. To investigate whether these Ab2s could induce G250-TAA-specific cell-mediated immunity, delayed-type hypersensitivity (DTH) tests were carried out with G250 antigen-positive and/or -negative cells in the ears of BALB/c mice. Mice primed with Ab2 showed antigen-specific DTH responses, whereas no significant DTH response was observed with G250-negative cells. This antigen-specific DTH could be transferred to naive mice by lymphocytes harvested from Ab2-sensitized mice. In addition to the classical DTH responses observed 24 and 48 hr after tumor challenge, an early-phase antigen-specific hypersensitivity response was seen 2 hr after challenge. This early component of the specific hypersensitivity reaction but not the classical DTH could be transferred to naive mice by serum from Ab2-sensitized mice, indicating that the early reaction was due to serum factors. These findings demonstrate that all Ab2s induced tumor-specific cellular immune responses directed against human RCC, and suggest that they may be useful as RCC-TAA surrogates, i.e., as tumor vaccines for RCC patients.

Animals↗
PubMed1994

Vaccination with anti-idiotype antibodies mimicking a renal cell carcinoma-associated antigen induces tumor immunity.

We have previously isolated and characterized 6 different internal image mouse monoclonal anti-idiotype antibodies (Ab2) directed against the paratope of mouse monoclonal antibody G250 (MAbG250, Ab1), which specifically reacts with human renal cell carcinoma (RCC). These Ab2s (NUH31, 44, 51, 71, 82 and 91) demonstrated specificity for the combining site of Ab1, and appeared to recognize 2 partly overlapping idiotopes on Ab1. In this study, we further characterize the fine specificity of the Ab2, investigate whether the immunogenicity of Ab2 could be enhanced by conjugation to a carrier and investigate the anti-tumor efficacy of Ab3 sera in mice challenged with RCC. Immunization of animals with Ab2 conjugated to keyhole limpet hemocyanin as carrier protein resulted in a 2-fold increase in antigen-specific anti-anti-idiotype antibodies (Ab3) as compared with immunization using Ab2 alone. Specific reactivity was observed with antigen-positive cell lysates, and all Ab3 sera contained immunoglobulin resembling Ab1 (Ab1'), as shown by competitive Ab1-antigen binding assays. Fine-specificity studies of Ab3 sera revealed that the Ab2s can be divided into 4 mutually exclusive groups, showing that the 6 Ab2s recognize 4 slightly different idiotopes in the Ab1 binding pocket. Treatment of RCC-challenged mice with Ab3 sera resulted in significant tumor growth inhibition and lower tumor take rates as compared with control groups. Ab3 sera obtained from NUH-91-immunized animals showed superior characteristics as compared to the other Ab3 sera: no tumors remained after 5 weeks of Ab3-NUH91 treatment. Our findings indicate that the Ab2 elicit powerful anti-tumor effects in immune-competent animals.

Adjuvants, Immunologic↗
PubMed1994

Internal image anti-idiotype antibodies related to renal-cell carcinoma-associated antigen G250.

The potential usefulness of internal-image anti-idiotype antibodies (Ab2s) in modulating hosts' immune responses to tumor-associated antigen (TAA) have stimulated considerable interest in the development and characterization of Ab2s. Six different mouse monoclonal Ab2s (NUH31, 44, 51, 71, 82 and 91) were generated against murine monoclonal antibody G250 (MAbG250) which recognizes a human renal-cell carcinoma-associated antigen. All 6 Ab2s showed specificity for the MAbG250 paratope in Western-blot analysis. In inhibition assays, all Ab2s were able to compete with the nominal antigen, albeit with differing efficiency. Based on cross-blocking studies for idiotope mapping, the Ab2s could be divided into 2 groups (group I; NUH31, 51, 71, group 2; NUH44, 82, 91). However, cross-reactivity between these 2 groups was observed, indicating that they recognized partly overlapping epitopes on the paratope of MAbG250. Sera from rabbits immunized with Ab2s showed reactivity with G250 antigen-positive cell lysates, but not with antigen-negative cell lysates. Additional studies revealed that all Ab2s were able to induce anti-anti-idiotype antibodies resembling MAbG250 (Ab1'). These findings suggest that the Ab2s functionally mimic the original G250 antigen and may be of use in the immunotherapy of human renal-cell carcinoma.

Animals↗
PubMed1994

Therapeutic effects of monoclonal antibody G250, interferons and tumor necrosis factor, in mice with renal-cell carcinoma xenografts.

Because renal-cell carcinoma (RCC) is considered relatively resistant to radio- and chemotherapy, RCC patients may benefit from new treatment modalities, e.g. immunotherapy. In vitro and in vivo studies suggest that combinations of cytokines such as interferon gamma or interferon alpha (IFN-gamma, IFN-alpha) and tumor necrosis factor alpha (TNF-alpha) may act synergistically. In this study we tested whether a monoclonal antibody (MAb) G250, reactive with a RCC-associated antigen, showed anti-tumor effects in vivo in nude mice with established s.c. human RCC xenografts, and also whether this MAb could enhance the anti-tumor effect of combinations of IFNs and TNF-alpha. Treatment with combinations of IFN-alpha/TNF-alpha or IFN-gamma/TNF-alpha, or with MAb G250 alone, resulted in a significant inhibition of tumor growth. Treatment with MAb G250, in combination with IFN-gamma/TNF-alpha, did not result in an improve anti-tumor effect as compared to that of either treatment alone. In contrast, MAb G250 combined with IFN-alpha/TNF-alpha resulted in a significantly enhanced anti-tumor response. In one experiment, 3 out of 10 mice showed complete tumor regression, with no recurrence after 90 days. Large numbers of infiltrating macrophages were found surrounding viable and necrotic tumor tissue after treatment with G250 combined with IFN-alpha/TNF-alpha. These results suggest that combination therapy, consisting of IFN-alpha, TNF-alpha and MAbs, may have therapeutic value in the treatment of RCC.

Animals↗
PubMed1994

High energy shock waves induced increase in the local concentration of systemically given TNF-alpha.

The influence of high energy shock waves (HESW) on the local concentration of systemically given TNF-alpha was studied in a syngeneic rat bladder tumor model. 125I-TNF-alpha was injected intravenously and within 1 minute was followed by HESW tumor exposure. High energy shock waves were generated using an experimental shock wave emitter based on the Siemens Lithostar Plus. Administration of HESW to RBT323 tumors resulted in a 3-fold increase in uptake of 125I-TNF-alpha in the tumor compared with nontreated tumors, whereas the tissue distribution and pharmacokinetics of nontumor tissue were similar irrespective of HESW exposure. These results demonstrate that HESW administration leads to an increase in the local concentration of a systemically given drug. The capacity of HESW to increase local drug concentrations will be of importance in designing more effective combined treatment strategies.

Animals↗
PubMed1993

Antibody localization in human renal cell carcinoma: a phase I study of monoclonal antibody G250.

PURPOSE: To define the imaging and biodistribution characteristics of iodine 131-labeled monoclonal antibody (mAb) G250 (131I-mAbG250), which recognizes a cell-surface antigen expressed by human renal cell carcinoma (RCC). PATIENTS AND METHODS: G250 is a cell-surface antigen recognized by mAbG250 expressed by RCC but not detected in normal kidney. Clear-cell RCC, the most frequent form of RCC, shows homogeneous expression of G250, whereas non-clear-cell RCC and cancers derived from other organs generally do not express G250. Expression in normal tissues is highly restricted and limited to large bile ducts and gastric epithelium. 131I-mAbG250 was administered intravenously (IV) to 16 patients with RCC 7 to 8 days before surgery at five dose levels, with at least three patients entered at each dose level. RESULTS: Clear tumor images were observed in 12 patients with G250-positive tumors and in one of three patients with G250-negative tumors. Imaged lesions in the peritoneal cavity were confirmed at surgery. The smallest lesion visualized was 8 mm in diameter. The specificity of 131I-mAbG250 localization to tumor tissue was established by radioactivity measurements, autoradiography, and immunohistochemistry of biopsied tissues, and technetium 99-human serum albumin blood-flow studies. The fraction of the injected 131I-mAbG250 dose per gram tumor (%ID/g tumor) localized in G250-positive tumors showed a broad range, but reached levels as high as 0.02% to 0.12%. CONCLUSION: 131I-mAbG250 localized specifically to G250 antigen-positive RCC and seems to have considerable potential as an imaging agent in RCC patients. 131I-mAbG250 uptake in the tumors, relative as well as absolute, are among the highest reported for tumor biopsies obtained 8 days after IV mAb administration. Based on the specific localization and high accumulation, mAb G250 may have therapeutic potential.

Adult↗
PubMed1991

Neutral glycosphingolipid expression in B-cell neoplasms.

The expression of neutral glycosphingolipids (GSL) in 37 B-cell neoplasms [7 acute lymphocytic leukemia (ALL), 5 Burkitt's lymphoma (BL), 7 chronic lymphocytic leukemia (CLL), 5 diffuse, poorly differentiated lymphoma (DPDL), 6 diffuse histiocytic lymphoma (DHL), 3 hairy-cell leukemia (HCL), and 4 multiple myeloma (MM)] was examined. Patterns of expression of simple (GlcCer, LacCer) and globo-series GSL (Gb3, Gb4) were found for each tumor type. In addition, pre-B ALL expressed the neo-lacto series GSL, paragloboside, which was not significantly seen at later stages of maturation. As a group, leukemias expressed about 10 times higher ratios of simple GSL to Globo-series GSL as compared to lymphomas, regardless of stage of differentiation. Significant amounts of GSL of other series were not found except in one CLL which contained asialo-GM2. GSL phenotype in these cells was not grossly affected by cell genotype since pre-B ALL containing Philadelphia chromosome t(9q;22q) translocations were similar to other ALL; and DHL with t(8q;14q) translocations had GSL patterns similar to other DHL samples and dissimilar to GSL patterns found in Burkitt's lymphomas with t(8q;14q). Differences in GSL expression among the different types of B-cell neoplasm suggested that GSL patterns form a phenotypic map that may complement the traditional glycoprotein immunophenotypic map and contribute to our understanding of the biology of these diseases and B-cell differentiation.

Antibodies, Monoclonal↗
PubMed1991

Monoclonal antibodies against Gal alpha 1-4Gal beta 1-4Glc (Pk, CD77) produced with a synthetic glycoconjugate as immunogen: reactivity with carbohydrates, with fresh frozen human tissues and hematopoietic tumors.

The purpose of this study was to isolate mouse monoclonal antibodies (MAbs) recognizing Gal alpha 1-4Gal beta 1-4Glc (Pk, CD77), which has been described as a Burkitt's-lymphoma-associated antigen. Three IgGI MAbs reactive with Pk were developed using a synthetic glycoconjugate as immunogen and a filter immunoplaque screening assay. One MAb (PK67) was characterized by immuno-thin-layer chromatography, ELISA and competition assays using neutral glycolipids from various sources and a variety of carbohydrates and glycoproteins. Epitope analysis showed that all 3 carbohydrates moieties are required in PK67 binding. No cross-reactivity was observed with closely related carbohydrate structures, with the exception of Gal alpha 1-4Gal beta 1-4GlcNAc. However, the reactivity with this structure was several orders of magnitude lower than with Pk. Immunohistochemical analysis of fresh-frozen tissue specimens showed that Gb3 is widely expressed: prominent staining was observed in many normal tissues, e.g., kidney and gastric tissue and on capillary endothelial cells. In lymph nodes, very weak staining of a few B cells was observed. Flow cytometric analysis of hematopoietic neoplasms showed Gb3 expression on B-cell neoplasms, particularly those with committed B-cell phenotype indicating that, in addition to earlier reports of Gb3 expression on Burkitt's lymphoma, Gb3 is present on other committed B-cell neoplasms.

Animals↗
PubMed1991

A monoclonal antibody for terminal beta-galactose. Use in analysis of glycosphingolipids.

A monoclonal antibody (mAb 8281) specific for the terminal beta-galactose (beta Gal) of glycosphingolipids (GSL) and glycoproteins was produced from mice immunized with lipid extract from fresh acute lymphocytic leukemia (ALL) cells. Immuno-thin layer chromatography (ITLC) and competition assays with purified neutral GSL standards, free sugars, and synthetic neoglycoproteins showed mAb 8281 to be strongly reactive with LacCer, GalCer and Gal-beta-O-(CH3)2S(CH3)2-CONH-(Gal-beta-O-CETE) linked to bovine serum albumin (BSA). The penultimate sugar also played a role in binding. The antibody was not reactive with carbohydrates with terminal alpha Gal structures and unrelated terminal moieties. Indirect immunoperoxidase staining and flow cytometry with mAb 8281 demonstrated positive staining on numerous tissues, including smooth muscle, gastrointestinal mucosa, lymph node B cells and monocytes. ITLC analysis of the GSL composition of fresh B cell neoplasms using mAb 8281 confirmed the presence of lactosylceramide and galactosylceramide in neoplasms of varying stages of differentiation. Because of its specificity for terminal beta Gal carbohydrate residues, mAb 8281 may be useful in structural and functional analyses of GSL.

Animals↗
PubMed1990

Expression of intermediate-sized filaments in developing and adult human kidney and in renal cell carcinoma.

We studied the distribution of intermediate-sized filaments in developing and adult kidneys and renal cell carcinoma (RCC) by indirect immunohistochemistry, using a pan-cytokeratin mouse monoclonal antibody (MAb), chain-specific anti-cytokeratin MAb, and anti-vimentin and anti-desmin MAb, to resolve controversy concerning intermediate-sized filament expression in the kidney. With the pan-cytokeratin MAb, cytokeratin expression was detectable in all stages of nephron development, starting with expression in the renal vesicles, the progenitors of the glomeruli, proximal tubules, Henle's loop, and part of the distal tubules. Using chain-specific anti-cytokeratin MAb, cytokeratin 8 and 18 expression was demonstrated in all developmental structures of the nephron, whereas cytokeratin 19 expression was more complex. None of the nephrogenic blastema cells from which the renal vesicles arise expressed cytokeratins. Transient expression of vimentin and cytokeratin 19 was observed in differentiating collecting ducts and proximal tubule cells at the S-shaped stage of nephron development, respectively. In RCC, cytokeratin expression closely resembled that of the mature proximal tubule, i.e., RCC cells expressed cytokeratins 8 and 18. However, in a subset of RCC additional cytokeratin 19 expression was noted. In addition, all except one RCC showed co-expression of cytokeratins and vimentin.

Adult↗
PubMed1988

Relationship between DNA ploidy, antigen expression and survival in renal cell carcinoma.

Tumor ploidy and expression of renal differentiation antigens as recognized by a previously described series of monoclonal antibodies (MAbs) (RC2, RC3, RC4, RC38, RC69, RC154 and G250) were assessed in 48 renal-cell carcinomas. A positive association was found between aneuploidy and development of metastases. Aneuploid tumors showed a loss of antigen expression more frequently than diploid tumors. This difference was statistically significant for antigens recognized by RC3 and RC69. Loss of RC154 reactivity was associated with increased metastatic potential. Clinical stage was the most powerful single prognostic variable but ploidy and RC3 reactivity carried additional prognostic information.

Actuarial Analysis↗
PubMed1988

Renal oncocytoma: a report of two cases with immunohistochemical evaluation.

Two cases of renal oncocytoma are characterized by histologic electron microscopic, and immunohistochemical evaluation. In one case there was a coexistent renal cell carcinoma. The immunophenotype of the oncocytes provide evidence for an origin from the distal nephron. The results indicate that immunohistochemical methods can be helpful in discriminating renal oncocytoma from (granular type) renal cell carcinoma.

Adenoma↗
PubMed1988

Perfusion of tumor-bearing kidneys as a model for scintigraphic screening of monoclonal antibodies.

Tumor-bearing human kidneys were used in an ex vivo perfusion model to screen monoclonal antibodies, recognizing renal cell carcinoma-associated antigens for diagnostic potential in vivo. Perfusion of tumor-bearing kidneys with 99mTc-labeled G250 and RC38 antibody resulted in visualization of the tumor, whereas perfusion with two other monoclonal antibodies, RC2 and RC4, did not lead to tumor visualization. Uptake of radiolabel in normal kidney tissue was low for G250 and RC38 antibody. Tumor-to-kidney tissue ratios after perfusion with G250 and RC38 antibody were 2.7 and 2.2, respectively. After rinsing for 3 hr with unlabeled perfusion fluid the tumor-to-kidney tissue ratios increased to 8.6 for G250 antibody and to 2.7 for RC38 antibody. We conclude that perfusion of tumor-bearing human kidneys with radiolabeled monoclonal antibodies is a relatively simple way to evaluate renal cell carcinoma associated monoclonal antibodies as diagnostic agents in vivo.

Antibodies, Monoclonal↗
PubMed1986

Monoclonal antibody G 250 recognizes a determinant present in renal-cell carcinoma and absent from normal kidney.

This report describes a monoclonal antibody designated G 250, subclass IgGl, that recognizes an antigen preferentially expressed on cell membranes of renal-cell carcinoma cells (RCC) and not expressed in normal proximal tubular epithelium. G 250 antibody reacted with 46 of 47 primary RCC, with 7 of 8 RCC metastases and with a few other malignant tumors. The staining pattern of G 250 differs from that of other RCC-related antibodies described. Preliminary experiments show that this antibody can be used to visualize RCC xenografts in nude mice by immunoscintigraphy.

Animals↗
PubMed1986

Immunohistochemical analysis of monoclonal antibodies to renal antigens. Application in the diagnosis of renal cell carcinoma.

Four mouse monoclonal antibodies reacting with renal proximal epithelium were characterized on normal adult tissues, fetal kidneys, and various malignancies. These four antibodies were found to react with renal cell carcinomas (RCCs) but not with a variety of other tumors. Three antibodies react only with some primary RCCs and not with metastatic RCCs. The fourth antibody, RC 38, reacts with 46 of 47 primary RCCs tested and with 8 of 13 RCC metastases. No reaction was seen with 179 tumors of various origin, which indicates that this antibody is very useful in diagnosing RCC.

Adenoma↗