Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Murine monoclonal antibody HRS-4 (Ab1), which defines the cell-bound and soluble CD30 antigen associated with Hodgkin's lymphoma, was used to generate monoclonal anti-idiotypic antibodies (Ab2) in syngeneic BALB/c mice. Murine monoclonal Ab2 14G9 and Ab2 9G10 directed against HRS-4 were shown to be anti-idiotypic Ab2 beta carrying the internal image of the CD30 antigen. These antibodies bound specifically to HRS-4 and effectively inhibited binding of HRS-4 to a CD30 antigen preparation at concentrations as low as 50 ng/ml. KLH-coupled Ab2 beta 14G9 and 9G10 induced in BALB/c mice and New Zealand white rabbits a specific polyclonal humoral response against the 120 kDa band of the CD30 antigen. Moreover, BALB/c mice immunized i.p. with KLH-coupled 14G9 and 9G10 exhibited a statistically significant (p less than 0.01) delayed-type hypersensitivity reaction against CD30 expressing Hodgkin-derived L540-cells. We conclude from these data that Ab2 beta 14G9 and 9G10, mimicking structures of the nominal CD30 antigen, are capable of inducing a CD30-specific T-cell- and B-cell-mediated immune response in mice and even across species barriers in rabbits. These CD30 anti-id antibodies may hold promise for use as vaccines against CD30-antigen-expressing lymphomas.
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PMID:Anti-idiotype vaccine against Hodgkin's lymphoma: induction of B- and T-cell immunity across species barriers against CD30 antigen by murine monoclonal internal image antibodies. 131

Immunoscintigraphy (IS) using the HRS-3 Hodgkin associated monoclonal antibody (MoAb) was performed in 18 patients with Hodgkin's Disease (HD) at staging or restaging. Either F(ab')2 fragments (14 patients) or whole HRS-3 (4 patients) labeled with 77-260 Mbq 131-I were used. Whole body images, including anterior and posterior views, were taken from a digital gamma camera, within 4 to 8 hours after injection and then daily for 5 days. In one patient IS was discontinued due to iodine intolerance. Seventeen patients were evaluable: 14 showed a true positive result including 2 cases which were reviewed as anaplastic large cell lymphoma (ALCL). Nodal, splenic, bone marrow and muscle involvements were imaged, many of these sites were previously unsuspected. In 7 patients with true positive findings the Pressman Specificity Index, as measured from biopsied material, ranged from 1.5-3 in 4 patients and from 5 to greater than 100 in 3 patients. Imaging was equivocal or failed in 1 patient (lymph nodes). In 2 patients, IS imaging was truly negative due to the absence of active HD, and a false negative result occurred once (inguinal node). In none of the patients a false positive image was observed. In order to rule out non-specific iodine uptake a control, anti-ACE MoAb, labeled with 125-Iodine was injected simultaneously in 10 patients. The evaluation of the study gave a sensitivity of 87% and a good specificity. IS using radioiodine labeled MoAbs is feasible and represents a reliable non-invasive diagnostic method for the staging and follow-up of HD and ALCL.
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PMID:Immunoscintigraphy in Hodgkin's disease and anaplastic large cell lymphomas: results in 18 patients using the iodine radiolabeled monoclonal antibody HRS-3. 133 72

Paraffin sections from 21 cases of Hodgkin's disease (HD), 28 cases of non-Hodgkin's lymphomas (NHL) and 34 cases of non-specific reactive lymphadenitides occurring in childhood were examined for the presence of the Epstein-Barr Virus (EBV)-encoded Latent Membrane Protein (LMP) using a double layer immunohistochemical method. LMP was detected in 12/21 (57%) cases of HD but not in NHL or reactive lymph nodes. LMP reactivity was restricted to Reed-Sternberg and Hodgkin's (HRS) cells in 4 of 9 (45%) cases of nodular sclerosis (NS), 6 of 9 (66%) cases of mixed cellularity (MC) and 2 of 2 (100%) cases of lymphocyte depletion (LD) while it was undetectable in the single case of lymphocyte predominance (LD) subtype. These results provide further evidence for an association between EBV and Hodgkin's disease, and they show that LMP expression occurs more frequently in the clinically more aggressive subtypes of HD. Furthermore, in view of the in vitro transforming potential of the LMP protein, the exclusive immunolocalization of LMP in HRS cells, suggests that EBV may be involved in the pathogenesis of a proportion of cases of HD.
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PMID:Expression of the Epstein-Barr virus encoded latent membrane protein in tumor cells of Hodgkin's disease occurring in childhood. 136 66

The murine monoclonal antibody HRS-3 (Ab1; isotype IgG1-Kappa), that defines the CD30 antigen (m.w. 120,000) expressed by Hodgkin-Reed Sternberg cells was used to generate monoclonal anti-idiotype antibodies (Ab2) in syngeneic BALB/c mice. Ab2 were selected on the basis of their binding to HRS-3 immunoglobulin and F(ab')2 fragments and lack of reactivity with the whole immunoglobulin or F(ab')2 fragments of unrelated monoclonal antibodies of the same isotype and allotype. Such a putative anti-idiotypic Ab2, was designated antibody 12D3 and further characterized. 12D3 bound to the paratope of HRS-3, as determined by a 85% inhibition of binding of biotinylated HRS-3 to the cell surface of the CD30 positive Hodgkin cell line L450, and to semipurified CD30 positive cell lysates thereof at a concentration as low as 50 ng/well. These results demonstrate that 12D3 binds at or near the binding site of HRS-3 to the CD30 antigen. Purified 12D3 was coupled to keyhole limpet hemocyanine and used to immunize BALB/c mice and rabbits in order to obtain an Ab3 which binds to the CD30 antigen. These immune sera inhibited the binding of biotinylated 12D3 with HRS-3. Moreover, they showed binding activity with the CD30 positive L540 Hodgkin cell line as well as with the L540 cell lysates, indicating that an anti-anti-idiotopic antibody (Ab3) shares idiotopes with Ab1 (HRS-3). These data suggest that antibody 12D3 may be useful in the generation of an anti-idiotype vaccine against Hodgkin's lymphomas.
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PMID:Idiotype vaccine against Hodgkin's lymphoma: generation and characterization of an anti-idiotypic monoclonal antibody against the Hodgkin-associated (anti-CD 30) monoclonal antibody HRS-3. 165 53

Three monoclonal antibodies which strongly bind to Hodgkin and Reed-Sternberg cells and two corresponding Fab' fragments were linked to deglycosylated ricin A chain (dg A) to evaluate their potential as immunotoxins for the treatment of Hodgkin's disease. Two of the antibodies, Ber-H2 and HRS-3, were shown to bind to the same epitope on the CD30 antigen, whereas the third antibody, IRac, bound to a different antigen. None of the antibodies significantly cross-reacted with normal human tissues as judged by indirect immunofluorescence and immunoperoxidase analyses on frozen sections from 28 normal tissues. All three antibodies formed potent and specific immunotoxins. They inhibited protein synthesis of the L540 Hodgkin's disease cell line in vitro by 50% at concentrations of 1 x 10(-11) M for IRac.dgA, 9 x 10(-11) M for HRS-3.dgA, and 2 x 10(-10) M for Ber-H2.dgA. HRS-3 Fab' and IRac Fab' immunotoxins were 7.8- and 60-fold less cytotoxic, respectively, than their intact counterparts in vitro. In vivo, a single i.v. injection of a dose of Ber-H2.dgA, HRS-3.dgA, or IRac.dgA corresponding to 40% of the LD50 induced lasting complete remissions in 38, 44, and 50%, respectively, of mice with solid s.c. L540 tumors of 60 to 80 mm3 size (0.5-cm diameter). At equivalent dosage (40% of the LD50), the HRS-3 Fab'.dgA and the IRac Fab'.dgA both induced lasting complete remissions in 25% of the mice, although the HRS-3 Fab'.dgA was significantly superior to IRac Fab'.dgA at retarding tumor growth in the remaining animals. The effectiveness of the immunotoxins depended on the size of the tumor at the time of injection, since IRac.dgA treatment induced complete remissions in 100% of mice with small tumors (10 to 20 mm3, approximately 0.3 cm in diameter) but only 13% of mice with larger tumors of 400 to 600 mm3 (approximately 1 cm in diameter). Tumors which regrew after IRac.dgA treatment mainly consisted of antigen-deficient mutants having reduced sensitivity to IRac.dgA but normal sensitivity to HRS-3.dgA. It is concluded that HRS-3.dgA, HRS-3 Fab'.dgA, and IRac.dgA are candidates for the treatment of Hodgkin's disease in humans.
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PMID:Antitumor effects of ricin A chain immunotoxins prepared from intact antibodies and Fab' fragments on solid human Hodgkin's disease tumors in mice. 169 51

The Hodgkin associated monoclonal antibody (Mab) HRS-1 reacts with Hodgkin and Reed-Sternberg cells (HR-S) in all HD subtypes. HRS-1 Mab was labelled with radioiodine and injected into 10 patients for immunoscintigraphy (IS). Seven patients were injected with HRS-1 Mab radiolabelled with 131I and three patients were injected with HRS-1 Mab labelled with 123I. A control anti-alpha-fetoprotein (anti-AFP) Mab was radiolabelled with another iodine isotope and was injected simultaneously in five cases. Six out of eight patients with proven HD had a true positive scan (nodal, splenic and bony involvement). Imaging was equivocal or failed in the two other patients. In the last two patients IS imaging was truly negative due to the absence of residual HD in one patient and to an erroneous histological diagnosis of HD in another patient. These results, although preliminary, demonstrate that IS with radioiodine-labelled HRS-1 Mab is feasible and may prove to be informative in the staging of HD.
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PMID:Immunoscintigraphy of Hodgkin's disease: in vivo use of radiolabelled monoclonal antibodies derived from Hodgkin cell lines. 169 88

Five monoclonal CD30 antibodies and two Fab' fragments were linked to deglycosylated ricin A chain (dgA), and their potential as immunotoxins for the treatment of Hodgkin's disease was evaluated. Cross-blocking experiments demonstrated that HRS-1, HRS-3, HRS-4, and Ber-H2 recognize the same epitope on the CD30 antigen and that Ki-1 binds to a different epitope. Scatchard analyses showed that HRS-3, HRS-4, and Ber-H2 bound strongly to L540 Hodgkin cells (Kd 15, 7, and 14 nM, respectively), whereas HRS-1 and Ki-1 bound more weakly (Kd 160 and 380 nM, respectively). The different affinities of the antibodies correlated closely with their cytotoxic potency as immunotoxins. HRS-3.dgA, HRS-4.dgA, and Ber-H2.dgA inhibited the protein synthesis of L540 cells by 50% at concentrations of 0.9-2.0 x 10(-10) M, whereas HRS-1.dgA and Ki-1.dgA were about 100 times less potent with 50% inhibitory concentrations of 0.8-1.0 x 10(-8) M. The most effective immunotoxins, HRS-3.dgA and HRS-4.dgA, were only 15 times less toxic than ricin itself. HRS-3 Fab'.dgA and HRS-4 Fab'.dgA were 7.8 and 3 times less potent than their IgG.dgA counterparts with 50% inhibitory concentrations of 7 x 10(-10) and 3 x 10(-10) M, respectively. Staining of human tissues revealed an unexpected cross-reactivity of HRS-4 with pancreatic cells of malignant and nonmalignant origin. HRS-1, HRS-3, Ber-H2, and Ki-1 showed very little cross-reactivity with any normal human tissues. It is concluded that HRS-3.dgA and HRS-3 Fab'.dgA are the immunotoxins of choice for in vivo therapy.
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PMID:Evaluation of ricin A chain-containing immunotoxins directed against the CD30 antigen as potential reagents for the treatment of Hodgkin's disease. 215 74

The bispecific monoclonal antibody (Bi-MAb) HRS-3/AP-1 was developed by somatic hybridization of the 2 mouse hybridoma cell lines HRS-3 and AP-1, which produce monoclonal antibodies with reactivity against the Hodgkin's- and Reed-Sternberg cell-associated CD30 antigen and alkaline phosphatase, respectively. After an active incubation with alkaline phosphatase, respectively. After an active incubation with alkaline phosphatase, purified whole immunoglobulin molecules and F(ab')2 fragments of the Bi-MAb were equally effective in converting a relatively noncytotoxic prodrug, mitomycin phosphate (MOP), into mitomycin alcohol, which was 100 times more toxic to the Hodgkin's- and Reed-Sternberg cell line L540 (CD30+) than MOP. The cytotoxic activity of MOP was unaffected when the cells were pretreated with either the Bi-MAb or the enzyme alone. The Bi-MAb HRS-3/AP-1 did not bind to HPB-ALL cells (CD30-) and was not able to activate MOP on these cells. In cocultivation experiments with HPB-ALL and L540 cells, the activation of MOP by the Bi-MAb HRS-3/AP-1 and alkaline phosphatase led to considerable cytotoxicity against the antigen-negative bystander cells. Thus, this immunotherapeutic approach might be effective in tumors in which not all the tumor cells express the respective tumor antigen.
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PMID:Specific activation of the prodrug mitomycin phosphate by a bispecific anti-CD30/anti-alkaline phosphatase monoclonal antibody. 217 12

The Hodgkin- and Reed-Sternberg cell associated monoclonal antibody HRS-1 was labeled with radioactive iodine and injected into 6 patients with Hodgkin's lymphoma for immunoscintigraphic imaging. Four of five patients who received 131I-labeled HRS-1 had a positive immunoscintigram. In the sixth patient, the HRS-1 Mab was labeled with 123I in order to utilize tomoscintigraphy instead of linear scintigraphy. Bony disease was demonstrated by immunoscintigraphy in this patient. These preliminary results demonstrate that immunoscintigraphy with iodine-labeled HRS-1 Mab is feasible and informative in Hodgkin's lymphoma. The real clinical value of immunoscintigraphy in Hodgkin's lymphoma must be determined in a larger series of patients. Several modifications of the technique such as the use of Fab or F(ab')2 fragments should further improve the results.
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PMID:[In vivo imaging of Hodgkin's lymphomas using monoclonal antibodies]. 255 58

The Hodgkin Reed-Sternberg (HRS-1) monoclonal antibody (Mab) was raised against the L 428 Hodgkin's disease (HD) cell line. The HRS-1 Mab was labeled with radioactive iodine and injected into six patients with Hodgkin's disease of varied histological subtypes for immunoscintigraphic imaging. In five patients, the HRS-1 Mab was labeled with 131I; a control anti-alpha-fetoprotein (AFP) Mab was injected simultaneously in two of these five cases. Four of five patients had a positive scan (nodal, splenic and hepatic involvements), the results in the fifth patient being equivocal. In the sixth patient, the HRS-1 Mab was labeled with 123I in order to utilize tomoscintigraphy instead of linear scintigraphy. Although the immunoscintigraphy (IS) was performed secondary to effective chemotherapy, images of bony disease were demonstrated. These preliminary results demonstrate that IS with iodine-labeled HRS-1 Mab is feasible and informative in Hodgkin's lymphoma. The real clinical value and the specificity of IS deserves confirmation in a larger series of patients. Several techniques such as the use of Fab or F(ab')2 fragments should further improve the results.
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PMID:Radiolabeled monoclonal antibodies against Reed-Sternberg cells for in vivo imaging of Hodgkin's disease by immunoscintigraphy. 260 43


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