Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoradiography has shown marked heterogeneous distribution of radioactivity in all ten radiolabeled monoclonal antibody/tumor combinations evaluated by our laboratories for radioimmunotherapy (RIT) in mice. Quantitative autoradiography was performed on two of these combinations (131I-B72.3/colorectal carcinoma and 131I-LYM-1/Raji B-cell lymphoma) to obtain a correlation of film density with radiolabeled antibody distribution. Through the use of sectioned mini-thermoluminescent dosimeter(s) (TLD) or micro-TLD, isodose curves were generated from the film gradient density lines. A computer program was written to compare theoretical absorbed dose calculations to measured micro-TLD values. First-order agreement was reached for both antibody/tumor systems: (a) B72.3/colorectal system--810 cGy measured/824 cGy calculated per 200 microCi injected and (b) LYM-1/lymphoma system--1,740 cGy measured/1,580 cGy calculated per 656 microCi injected (1 cGy = 1 rad). Additionally, the measured absorbed dose heterogeneity over a 500-micron length of up to 400% which suggests that the use of quantitative autoradiography is necessary in order to correctly determine the underlying radiobiological effects of RIT. Theoretical computer modeling based on similar autoradiographic activity distributions has also provided a convenient means of assessing absorbed dose variation patterns from other radiolabels such as 90Y.
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PMID:Direct dose confirmation of quantitative autoradiography with micro-TLD measurements for radioimmunotherapy. 326 79

Experimental studies of I-131-LYM-1 MoAb radioimmunotherapy (RIT) and LYM-1 MoAb immunotherapy (IT) were performed in 23 implanted nude mice model. 1 x 10(7) human B-cell lymphoma cells (Raji Burkitt's cells) were injected subcutaneously into the thigh. Three weeks later, they were divided into four groups: Group A (N = 6), as control group; Group B (N = 5), received LYM-1 MoAb 60 micrograms, as IT group; Group C (N = 7), received I-131-LYM-1 MoAb 120 mu ci; and Group D (N = 5), received I-131-LYM-1 MoAb 240 mu ci. Radioimaging was performed on day 7,8,9 postinjection. Tumor growth after 30 days was as follows: Group A, from 0.040 +/- 0.091 CM3 to 7.638 +/- 5.925; Group B, from 0.326 +/- 0.315 to 4.498 +/- 2.572; Group C, from 0.632 +/- 0.449 to 3.330 +/- 4.875; Group D, from 0.490 +/- 0.531 to 2.352 +/- 2.188. When converted to Relative Increase of Tumor Volume (Times-X): The tumor in Group A increased 4346.19 X; in Group B 312.68 X; in Group C 15.94 X; and in Group D 8.36 X. Significant differences were noted between Groups A and B (p less than 0.05), A and C (p less than 0.025), A and D (p less than 0.025), B and C (p less than 0.025) and B and D (p less than 0.025). The difference between Group C and D was insignificant (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[I-131-LYM-1 MoAb radioimmunotherapy and LYM-1 MoAb immunotherapy in implanted nude mice model]. 326 32

Human B cell lymphoma (Raji) growing in athymic, nude mice has been successfully treated with a single pulse dose of 131I-labeled monoclonal antibody (Lym-1) specific for this tumor. Sequential in vivo measurements of phosphate metabolites in the tumors by 31P surface coil nuclear magnetic resonance showed a significant initial decrease of phosphocreatine following radioimmunotherapy. Diminution of relative ATP to Pi peak area ratio suggesting tissue damage occurred within 3-4 days. The contribution from metabolites resonating at ca 3.8 ppm (putative sugar phosphate region) increased. There was no significant change in pH either as a function of tumor volume or treatment. The sequence of alterations of nuclear magnetic resonance spectra from tumors of treated mice were strikingly different from sequential nuclear magnetic resonance spectra obtained from tumors of control mice. These observations lead us to conclude that 31P surface coil nuclear magnetic resonance is a promising non-invasive method for assessing and predicting the efficacy of radioimmunotherapy. Further spatial discrimination of the region of tissue observed by the surface coil nuclear magnetic resonance experiment is under exploration in an effort to increase the utility of these methods.
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PMID:Radioimmunotherapy of human lymphoma in athymic, nude mice as monitored by 31P nuclear magnetic resonance. 387 32

The Epstein-Barr virus-determined nuclear antigen (EBNA) was purified 700-fold to apparent homogeneity from Raji and Namalwa cell extracts by a three-step procedure involving heat treatment, DNA-cellulose chromatography, and hydroxyapatite chromatography. Acid-fixed nuclear binding and complement fixation were used to monitor antigenic specificity. Purified EBNA was also capable of specifically inhibiting the regular anticomplement immunofluorescence reaction for EBNA against Raji target cells. The purified antigen had a molecular weight of 170,000 to 200,000. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, it yielded a single 48,000-dalton (48K) monomer. An EBNA-associated protein was also purified from the same cell extract. It had a molecular weight of about 200,000 and yielded a single 53K protein band by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The same protein was also found in Epstein-Barr virus negative B-cell lymphoma lines. The two types of protein were characterized by amino acid composition and peptide mapping. The results showed that the 53K and 48K protein components have no long regions in common; this excludes that the smaller product arises by breakdown of the larger product. Residue distributions were different, but an excess of hydrophilic residues was found in both proteins, suggesting a certain overall similarity in properties. 53K components from different cell lines appeared to differ somewhat. Epstein-Barr virus-positive lines carry two 53K components, one of which may be a slightly modified 53K product. Immunocomplexing assay showed that the 48K, but not the 53K, protein carries EBNA specificity. In mixtures, the 53K protein is co-precipitated with the 48K protein. The data suggest that EBNA may form a complex with the 53K proten within the cell.
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PMID:Purification and biochemical characterization of the Epstein-Barr virus-determined nuclear antigen and an associated protein with a 53,000-dalton subunit. 615 79

Anti-idiotype monoclonal antibodies (Mabs) to mLL2, an anti-B-cell lymphoma and CD22-specific murine IgG2a-kappa Mab, were generated by hybridoma technology from splenocytes of Copenhagen rats immunized with mLL2 F(ab')2. Mab WN, an IgG2a-kappa, was selected based on its specific binding to mLL2 and not other IgG isotypes or anti-B-cell Mabs. In a radioimmunoassay, WN was found to inhibit the binding of 125I-labeled mLL2 to Raji cells and to have no effect on the binding of other B-cell-reactive antibodies. Using high performance liquid chromatography analysis, WN was shown to complex specifically with both mLL2 and mLL2 Fab'. Meanwhile, we have constructed chimeric (cLL2) and humanized (hLL2) versions of LL2. Both cLL2 and hLL2 were demonstrated to retain the original antigen specificity and affinity of mLL2 [S.O. Leung et al., Proc. Am. Assoc. Cancer Res., 2872 (abstract), 34: 481, 1993]. The specific binding of WN to either radioiodinated or peroxidase-conjugated mLL2 was inhibited in a dose-response manner, and to a similar extent by mLL2, cLL2, and hLL2. Since the mLL2 complementarity-determining regions are the only sequences common to mLL2, cLL2, and hLL2, the result confirms that WN is specific to the antigen-binding complementarity-determining regions. A WN binding assay is currently being evaluated as a substitute for the tedious, and sometimes inconsistent, Raji cell-binding assay for the determination of LL2 immunoreactivity. In conclusion, we have developed an anti-idiotype Mab, WN, to mLL2. Its potential use as a surrogate antigen for B-cell lymphoma is under investigation.
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PMID:Development and evaluation of the specificity of a rat monoclonal anti-idiotype antibody, WN, to an anti-B-cell lymphoma monoclonal antibody, LL2. 749 80

A panel of bispecific F(ab')2 antibodies (BsAb) have been constructed for delivering the ribosome-inactivating protein saporin to human B cell lymphoma. Each derivative was prepared with specificity for saporin and CD19, CD22, CD37, or immunoglobulin. In vitro studies measuring inhibition of [3H]leucine uptake by cultured Daudi and Raji cells demonstrated that, despite all BsAb capturing saporin on the cell surface, BsAb targeting through CD22 were far more cytotoxic than those functioning via CD19, CD37, or surface immunoglobulin. This exceptional activity of the CD22-specific BsAb appears to derive from its ability to deliver and accumulate saporin inside the target cells. Further studies showed that four CD22-specific BsAb all performed with equal potency and were able to increase saporin toxicity (50% inhibitory concentration) up to 1000-fold, from 2 x 10(-7) M to 2 x 10(-10) M. Pairs of anti-CD22 BsAb which recognized different nonblocking epitopes on the saporin molecule were able to bind saporin more avidly to the target cell and, as a consequence, increased cytotoxicity by at least an additional 10-fold, resulting in 50% inhibitory concentration for protein synthesis of 2 x 10(-11) M. These results suggest that selected combinations of BsAb which bind cooperatively to a toxin and the cell surface may provide an efficient way of delivering toxins to unwanted cells in patients.
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PMID:Delivery of saporin to human B-cell lymphoma using bispecific antibody: targeting via CD22 but not CD19, CD37, or immunoglobulin results in efficient killing. 768 48

LL2 is a murine monoclonal antibody IgG2a reactive with B cells and non-Hodgkin's B-cell lymphoma, which, in a radioiodinated form, induces responses in lymphoma patients [Goldenberg et al. (1991) J Clin Oncol 9:548-564]. In this report we identify LL2 as a member of the CD22 cluster. The molecular size of the antigen, its expression profile, and competitive blocking studies were used to establish this identification. By Western blot analysis and immunoprecipitation studies using the Raji Burkitt's lymphoma cell line metabolically labelled with [3H]leucine, the LL2 antigen was determined to correspond to a molecular mass of 140 kDa. The molecular mass of the LL2 antigen, and the B-cell-restricted reactivity of the LL2 antibody, were consistent with both the CD21 and CD22 clusters. To assess additional similarities and differences between LL2 and anti-CD22 and anti-CD21, the binding of these mAb to cultured cell lines, Nalm-6 and Molt-4, was compared by flow cytometry. The binding profile of LL2 on these cell lines was consistent with anti-CD22, but not anti-CD21. Sequential immunoprecipitation and cross-blocking studies with anti-CD22 monoclonal antibodies recognizing established CD22 epitopes were performed to confirm that LL2 reacts with CD22 and to determine which epitope LL2 recognizes. Binding of 131I-LL2 to Raji cells is inhibited over 90% by prior incubation of the target cells with unlabelled RFB4, indicating that LL2 belongs to the same epitope group as RFB4, i.e., epitope B.
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PMID:Epitope specificity of the anti-(B cell lymphoma) monoclonal antibody, LL2. 769 7

Recently G alpha 16, a new guanosine triphosphate (GTP) binding protein alpha subunit has been described to be specifically expressed in human hematopoietic cells. Expression of G alpha 16 was observed in human cell lines of myelomonocytic and T-lymphocytic origin, but not in human B-cell lines Raji and IM9. We studied the expression of G alpha 16 in human B cells corresponding to different stages of B-cell differentiation by means of reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. The human Burkitt's lymphoma cell lines Raji, Ramos, BJAB, the lymphoblastoid cell line SKW6.4, and the plasmocytoma cell line U266 were devoid of G alpha 16. In contrast, G alpha 16 was detected in the human progenitor B cell lines Reh and Nalm-6. Using the mu+, k- cell line BLIN-1 (pre-B cell phenotype) and its derived subclone 1E8 (surface mu+, k+; B-cell phenotype) G alpha 16 expression was found to disappear on transition from pre-B to B-cell differentiation stage. The analysis of a broad panel of human neoplastic B lymphocytes ranging from progenitor B-acute lymphatic leukemia (pre-pre-B-ALL), common acute leukemias (cALL), pre-B-ALL, mature B-ALL to low grade B-cell lymphoma (chronic lymphocytic leukemia of B-cell type, leukemic centrocytic non-Hodgkins lymphoma [NHL], hairy cell leukemia) showed that G alpha 16 expression is limited to progenitor and pre-B-ALL cells. Therefore, we conclude that within B-cell differentiation, G alpha 16 is expressed solely during early B cell ontogeny and downregulated during differentiation. Thus, G alpha 16 might be an important regulator involved in signaling processes in progenitor B cells.
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PMID:G protein subunit G alpha 16 expression is restricted to progenitor B cells during human B-cell differentiation. 770 90

LL2 is a murine monoclonal antibody (MAb) that has been shown to be effective for the diagnosis and treatment of patients with non-Hodgkin's B cell lymphoma. Studies have also shown that radiolabeled murine LL2 (mLL2) or mLL2 and fragments thereof coupled to Pseudomonas exotoxin (PE) can effectively target human B cell lymphoma in mice. We have obtained the DNA sequences encoding the VK and VH domains of mLL2, an IgG2a MAb, which were combined with their respective human kappa and IgG1 constant region domains and expressed in SP2/0 cells. Like its murine counterpart, the chimeric LL2 (cLL2) antibody is glycosylated in the light chain variable region. Chimerization did not interfere with the immunoreactivity of the antibody, as determined by a competitive binding assay, where either antibody shows equivalent inhibition of the binding of its counterpart to the Raji cell membrane surface antigen, CD22. Both antibodies bind and are rapidly internalized by Raji cells, whereas an irrelevant humanized antibody did not bind and was not internalized under similar conditions. The internalization rates of the bound murine or chimeric antibodies were nearly identical, with Ke values of 0.106 and 0.118 min-1 for mLL2 and cLL2, respectively. The observed close equivalence between the murine and chimeric antibodies suggests potential advantages of the latter as a less immunogenic agent. Studies are currently underway to evaluate the chimeric antibody as a potential therapeutic immunoconjugate.
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PMID:Chimerization of LL2, a rapidly internalizing antibody specific for B cell lymphoma. 773 71

The epitopes Tn and sialosyl-Tn are expressed on erythrocytes of individuals with a very rare blood group, who often suffer from "Tn syndrome." We surveyed expression of Tn and sialosyl-Tn in normal blood cells, malignant transformed cells, and progenitor stem cells from bone marrow (BM). An anti-Tn antibody, IE3, and an anti-sialosyl-Tn antibody, TKH2, were used in this study. TKH2 reacted with erythroblasts, B cells, and a subset of CD4+ cells; but not with erythrocytes. Erythroblastic cell lines (K562, HEL, and UT7/EPO) and B-cell lines (Daudi, Raji, and B-cell lines transformed by Epstein-Barr virus) showed reactivity to TKH2. Similar results from the reactivity of TKH2 with transformed cells from leukemia patients and lymphoma patients were obtained; TKH2 reacted with blasts from erythroleukemia (M6; for 4 of 4 cases) and with lymphocytes from B-cell chronic lymphocytic leukemia (3 of 3), B-cell lymphoma (5 of 5), and CD4+ adult T-cell leukemia (4 of 4), but did not react with blasts from acute myeloid leukemia (M0 to M5; 0 of 22) or acute lymphoid leukemia (B-lymphoid leukemia, 0 of 11; T-lymphoid leukemia, 0 of 2; undifferentiated leukemia, 0 of 1). IE3 did not react with all of the tested cells. CD2-CD19-TKH2+ normal BM cells (BMC) contained blasts and various maturation stages of erythroblasts. The TKH2+ cells produced a large number of colony-forming unit-erythroid (CFU-E) colonies, whereas they produced a small number of burst-forming unit-erythroid colonies and CFU-granulocyte-macrophage colonies. CD34+ normal BMC did not express Tn and sialosyl-Tn. These findings suggest that sialosyl-Tn expresses in CFU-E to erythroblasts.
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PMID:Expression of sialosyl-Tn in colony-forming unit-erythroid, erythroblasts, B cells, and a subset of CD4+ cells. 790 75


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