UMLS:C0019829 - FACTA Search

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Query: UMLS:C0019829 (Hodgkin's disease)
30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The two monoclonal antibodies HRS-1 and HRS-2, which were obtained after immunization with the Hodgkin's derived cell line L428, detect different epitopes on a 120 kd antigen. This antigen is present on Hodgkin- and Reed-Sternberg (H&RS) cells in all subtypes of Hodgkin's lymphoma and on large cell anaplastic non-Hodgkin's lymphomas. The H&RS- associated 120 kd antigen appears to be a non-lineage specific activation antigen, as it is not present on normal B and T lymphocytes or monocytes, but appears on these cells after activation. Because of their restricted reactivity with H&RS cells, HRS-1 and HRS-2 alone or in combination may be helpful for immunoimaging and immunotherapy of Hodgkin's lymphomas.
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PMID:Hodgkin and Reed-Sternberg cell associated monoclonal antibodies HRS-1 and HRS-2 react with activated cells of lymphoid and monocytoid origin. 336 33

CD30L, the ligand for the activation antigen CD30, is a member of the tumor necrosis factor family of cytokines. Binding of CD30L to CD30, which is a member of the nerve growth factor/tumor necrosis factor receptor family, induces proliferation in peripheral blood lymphocytes and Hodgkin's derived cell lines with a T-cell phenotype such as HDLM-2 and L540, while cell lines derived from anaplastic large cell lymphomas, such as Karpas 299, undergo cell death. In order to investigate whether mutations of the CD30 antigen are responsible for these opposite effects, we cloned the open reading frame of CD30 cDNAs from the cell lines L540 and Karpas 299 and from peripheral blood lymphocytes by reverse transcriptase polymerase chain reaction. Sequencing of independent plasmid clones revealed that these cells have a silent transition (A-->G) at position 771 of the open reading frame compared to the published sequence derived from the HTLV-1+ cell line HUT-102. As published data have shown that crosslinking of CD30 induces an elevation of cytosolic free calcium ([Ca2+]i) in TCR positive Jurkat cells, we have analysed the effect of crosslinking of CD30 on L540 and Karpas 299 cells. No elevations of [Ca2+]i have been observed in these cell lines after crosslinking of CD30 with HRS-4. We conclude (i) that the different functional effects of CD30 in PBL, L540 and Karpas 299 are not due to differences in the primary structure of the receptor; and (ii) that the different responses observed upon engagement with CD30L for the cell lines L540 and Karpas 299 do not correlate with differences in mobilization of [Ca2+]i after crosslinking of CD30.
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PMID:Opposite effects of the CD30 ligand are not due to CD30 mutations: results from cDNA cloning and sequence comparison of the CD30 antigen from different sources. 752 1

The CD30-activation marker was detected as the Hodgkin-associated Ki-I antigen and is regarded as a target for the treatment of Hodgkin patients with immunotoxins. The CD30 is released from tumor cells and this soluble CD30 (sCD30) is an indicator of the disease activity. Since the shedding of sCD30 may be influenced by antibodies, we produced 6 new CD30-specific antibodies (Ki-2 to Ki-7) for the purpose of finding antibodies that might inhibit the formation of sCD30. Ki-2 to Ki-7 and the other anti-CD30 antibodies Ki-I, Ber-H2, HeFi-I, M44, M67, HRS-I, HRS-4 and C10 were employed for epitope mapping. The binding of a particular radio-labeled anti-CD30 antibody to Hodgkin's-disease-derived L540 cells was completed by addition of the various non-labeled anti-CD30 antibodies. Three non-overlapping regions, expressing different antigen-specific determinants, could be defined on the extracellular part of the CD30 molecule. Cluster A of determinants was recognized by Ki-2, Ki-4, Ki-6 and Ki-7, Ber-H2, HRS-I and HRS-4, while cluster B was detected by Ki-I, Ki-5 and M67. Cluster C, which probably contains the binding site for the CD30 ligand, was defined by Ki-3, M44, HeFi-I and C10. Co-culture experiments of L540 cells with the various antibodies followed by the isolation of sCD30 from culture supernatant fluids revealed that the release of sCD30 was most strongly increased by Ki-I and weakly enhanced by Ki-2, Ki-3, Ki-5 and HeFi-I, whereas it was almost completely inhibited by Ki-4 and to a slightly lesser extent by Ber-H2.
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PMID:Shedding of the soluble form of CD30 from the Hodgkin-analogous cell line L540 is strongly inhibited by a new CD30-specific antibody (Ki-4). 753 Feb 38

The relative scarcity of Hodgkin (H) and Reed-Sternberg (RS) cells within biopsies from cases with Hodgkin's disease (HD) is an impediment to the analysis of the nature and function of these cells. Continuous cell lines as uniform and permanently available sources of cells provide a valid alternative. Development of HD cell lines has proven to be rather difficult when compared with the results on leukemia and Non-Hodgkin lymphoma cells. Only a few cell lines containing cells that resemble in-vivo H-RS cells have been established. Because the in-vitro culture conditions favor the self-propagation of residual normal cells, e.g. Epstein-Barr virus transformed B-lymphoblastoid cells or monocyte/macrophage monolayers, early attempts at culturing HD tissue resulted mainly in the generation of such cell lines. Even for the bona fide HD cell lines it is difficult to prove that the immortalized cells originated from an H-RS cell. These 13 HD cell lines have been extensively characterized in a large variety of aspects. These data have resulted in widely varying conclusions about the nature of the cell lines. It is apparent that all HD cell lines are unique among hematopoietic cell lines and are also different from one another. No conclusive evidence towards the origin of the cells has been obtained for some cell lines, while others could be operationally, albeit not always unequivocally, assigned to the T- or B-cell or monocyte-macrophage lineages. The overall phenotypes are often not concordant with those of normal hematopoietic cells; some cell lines show clearly mixed lineage attributes. The artifactual expansion of non-HRS cells in culture and the acquisition or loss of certain properties during the adaptation to culture systems cannot be excluded. There was also a bias for the establishment of cell lines from cases with advanced clinical stages, nodular sclerosing subtype and pleural effusions. The extensive analysis of a few cell lines has provided a wealth of information useful for the understanding of the biology of H-RS cells. The striking heterogeneity could be reflective of a biologically heterogeneous disease.
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PMID:Recent results on the biology of Hodgkin and Reed-Sternberg cells. II. Continuous cell lines. 768 80

Cross-linking of specific tumor antigens with the T-cell-associated CD3 and CD28 antigens can increase IL-2 secretion, proliferation and antigen-specific cytotoxicity in resting T cells. This cross-linking can be achieved effectively by bispecific monoclonal antibodies (BiMAb) with specificity for both the tumor antigen and CD3 or CD28 antigen, respectively. To take advantage of the enhanced activation of CD3 pre-activated T cells by additional activation via the CD28 antigen, BiMAb OKT3/HRS-3 with reactivity to both CD3 and the Hodgkin's-lymphoma-associated CD30 antigen and the BiMAb 15E8/HRS-3 with reactivity to both CD28 and CD30 antigen were generated by hybridoma fusion. Resting T cells, represented by Jurkat cells (CD3+/CD28+) were specifically activated to produce IL-2 by co-cultivation with an EBV-transformed B-cell line (LAZ509, CD30+/CD19+) only in the presence of the CD30/CD28 cross-linking BiMAb and an additional cross-linking anti-CD3/CD19 BiMAb (OKT3/6A4). Neither the cross-linking BiMAbs alone nor any combination of the monospecific parental MAbs induced a comparable IL-2 production by Jurkat cells in the presence of LAZ509. In addition, using a combination of these BiMAbs, an antigen-dependent cytotoxicity was induced by targeting APC-depleted peripheral blood lymphocytes to CD30+ L540 cells. T cells, previously specifically activated by CD3/CD30 in the presence of CD30 antigen, were cytotoxic to CD30+ cell lines only after incubation with BiMAb anti-CD28/CD30. Neither of the BiMAbs nor any of the parental antibodies induced a comparable effect. Our results indicate that such BiMAbs may offer a new approach for specific immunotherapy of Hodgkin's lymphoma, which takes advantage of cytokine secretion and cytotoxicity of activated T cells.
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PMID:CD30-antigen-specific targeting and activation of T cells via murine bispecific monoclonal antibodies against CD3 and CD28: potential use for the treatment of Hodgkin's lymphoma. 768 89

Paraffin sections from 22 cases of Hodgkin's disease (HD) and 30 cases of non-Hodgkin's lymphomas (NHL) occurring in childhood (3-15 years old) were examined for the presence of Epstein-Barr Virus (EBV) encoded EBER mRNAS and Latent Membrane Protein-1 (LMP-1) using RNA in situ hybridization (RISH) and immunohistochemistry, respectively. In 12/22 (54%) cases of HD the EBER transcripts were detected in most Reed-Sternberg and Hodgkin (HRS) cells as well as in some scattered smaller lymphoid cells. In all these cases the LMP-1 protein was detected exclusively in HRS cells. Three additional cases of HD were found to be EBER RISH positive only in a few scattered small lymphoid cells, the LMP-1 staining being negative in these cases. The EBER and LMP-1 positivity in HRS cells were present in 0/1 of lymphocyte predominant, 4/10 (40%) of nodular sclerosis and 8/11 (72%) of mixed cellularity of HD. No EBER RISH signal was found in tumor cells of the 30 cases of NHL. In four of them only a few scattered small lymphoid cells were EBER RISH positive. LMP-1 reactivity was not detected in any NHL. These results provide evidence for an association between EBV and a sizeable proportion of childhood Hodgkin's disease and show that this association is more frequent in mixed cellularity subtype. Furthermore, the detection of the LMP-1 protein in HRS cells in view of the LMP-1 transforming potential, suggests that EBV may be involved in the pathogenesis of a substantial proportion of cases of HD occurring in childhood.
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PMID:Frequent detection of Epstein-Barr virus (EBV), EBER transcripts and latent membrane protein-1 (LMP-1) in tumor cells in Hodgkin's disease arising in childhood. 774 35

In order to target NK cells against the Hodgkin's-derived cell line L540, we developed bispecific monoclonal antibodies (Bi-MAbs) by somatic hybridization of the 2 mouse hybridoma cell line HRS-3 and A9 which produce monoclonal antibodies (MAbs) with reactivity against the Hodgkin and Reed-Sternberg cell-associated CD30 antigen and the CD16 antigen (Fc gamma III receptor), respectively. The CD16 MAb-producing cell line A9 was selected as a partner for HRS-3 because of its efficiency in inducing lysis of the A9 hybridoma cells by resting NK cells. The hybrid hybridoma cell line HRS-3/A9 produced the supernatant with the strongest bispecific reactivity and was repeatedly subcloned and used for ascites production. Crude supernatant and purified HRS-3/A9 Bi-MAb triggered specific lysis of the CD30+ Hodgkin's-derived cell line L540, but not of the CD30- cell line HPB-ALL by unstimulated peripheral-blood lymphocytes and NK-cell-enriched populations. Moreover, treatment of SCID mice bearing heterotransplanted human Hodgkin's tumors with HRS-3/A9 and human peripheral blood lymphocytes induced specific complete tumor regression in 10/10 animals. We thus report successful tumor treatment in an in vivo model using NK-cell-associated Bi-MAbs and show that the Bi-MAb HRS-3/A9 is an efficient promoter of the anti-tumor effects of NK cells in vitro and in vivo.
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PMID:A CD16/CD30 bispecific monoclonal antibody induces lysis of Hodgkin's cells by unstimulated natural killer cells in vitro and in vivo. 824 80

The tumor-associated CD30 antigen is presently under study as a target for active specific immunotherapy of Hodgkin's lymphoma with anti-idiotypic antibodies. Internal image antibodies (Ab2 beta) 9G10 and 14G9 against the CD30-specific antibody HRS-4 (Ab1) have been described, which induce a CD30-specific T- and B-cell response in BALB/c mice and New Zealand white rabbits. In extension of this work, murine monoclonal anti-idiotypic Ab2 beta 9G10, mimicking structures of the nominal CD30 antigen, was used to generate monoclonal Ab3 in mice and polyclonal Ab3 in rabbits with specificity for CD30. The Ab2 beta 9G10-specific murine monoclonal Ab3 4A4 bound specifically to the 120-kDa band of CD30 present on Hodgkin cell lines and Hodgkin tumor tissue, and effectively inhibited binding of Ab1 HRS-4 to Ab2 9G10 as well as to CD30+ cells. Monoclonal Ab3 4A4 was cytotoxic for CD30+ cell lines in vitro and effectively prevented the s.c. growth of L540 cell tumors after passive i.v. administration in a SCID mouse tumor model. While this cytotoxic effect of the IgM subclass monoclonal Ab3 4A4 was due to complement activation, the murine monoclonal Ab1 HRS-4 and a polyclonal Ab3 preparation of IgG-subclass from New Zealand white rabbits were cytotoxic by an antibody-dependent cell-mediated mechanism in vitro. In conclusion, Ab2 beta 9G10 is able to induce a CD30-specific cytotoxic IgG and IgM response. Cytotoxicity was shown to be mediated by complement activation and antibody-dependent cell-mediated cytotoxicity in vitro and in vivo and across species barriers. Thus, the CD30-like Ab2 beta 9G10 may hold promise for effective active specific immunotherapy of human Hodgkin's lymphoma.
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PMID:CD30-specific AB1-AB2-AB3 internal image antibody network: potential use as anti-idiotype vaccine against Hodgkin's lymphoma. 838 37

We have investigated the immunohistochemical expression of beta2-microglobulin and HLA-DR proteins in Hodgkin's disease (HD) in relation to the expression of the EBV-encoded EBER1-2 mRNAs and the LMP-1 protein. beta2-microglobulin is expressed in association with MHC-I molecules on most nucleated cells and HLA-DR belongs to the MHC-II molecules which are expressed mostly on antigen-presenting cells. Formalin-fixed paraffin embedded tissue from 39 cases of lymphonodal HD were stained by immunohistochemistry for beta2-microglobulin, HLA-DR and LMP-1 proteins and by RNA in situ hybridization for EBER1-2 mRNAs. beta2-microglobulin positive staining was found in Reed-Sternberg and Hodgkin cells (HRS cells) in 18/39 cases of HD. HLA-DR positive staining was found in HRS cells in all cases of HD. EBER1-2 transcripts and LMP-1 protein were detected in HRS cells in 16/39 cases of HD. No correlation as found between the presence of EBER 1-2 transcripts or the LMP-1 protein and the detection of beta2-microglobulin and HLA-DR proteins in HD. Thus, EBV does not seem to use downregulation of MHC-I to avoid the T-cell cytotoxic immune response in HD. In addition, EBV does not seem to be the only factor responsible for the HLA-DR expression in HRS cells of HD, although it could participate in the induction of the expression of HLA-DR molecule in the EBV positive cases of HD.
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PMID:Major histocompatibility complex (MHC)-I and MHC-II expression in Hodgkin's disease in relation to the presence of Epstein-Barr Virus (EBV). 868 36

The values of five cellular morphometric parameters (longest and shortest cytoplasmic axis, cellular circumference, area and roundness coefficient) were compared between 20 Latent Membrane Protein 1 (LMP-1)-positive and an equal number of LMP-1-negative Reed-Sternberg and Hodgkin (HRS) cells for each of 13 cases of Hodgkin's disease (HD) occurring in children (aged 3-15 years); the presence of Epstein-Barr virus (EBV) encoded EBER mRNAs had previously been detected in all cases using RNA in situ hybridisation (RISH), while the presence of LMP-1 was immunohistochemically detected using the alkaline phosphatase-antialkaline phosphatase (APAAP) method. The longest and shortest axis, circumference and area were larger in LMP-1-positive than in LMP-1 negative HRS cells, while the roundness coefficient of LMP-positive HRS cells was smaller than that of LMP-1 negative cells. All differences were statistically highly significant when univariate (paired comparisons) t-test were used. Multivariate analysis (Hotelling's T2 test) showed all differences (except the roundness coefficient) to be significant both at the 5% and 1% level of significance. These results provide a numerical basis for the alteration brought by the expression of LMP-1 in the cellular skeleton of tumour (HRS) cells in EBV-related childhood HD cases.
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PMID:Morphologic differences between latent membrane protein-1 (LMP-1)-positive and negative tumour cells in Epstein-Barr virus (EBV)-related childhood Hodgkin's disease. A morphometric study. 873 67

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