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Biomedical subjects

A Hekman

Publications and source records attributed to A Hekman.

At least 37 records · Page 2Linked to original sources
PubMed1989

Potentiation by interleukin 2 of Burkitt's lymphoma therapy with anti-pan B (anti-CD19) monoclonal antibodies in a mouse xenotransplantation model.

To study the immunotherapeutic potential of monoclonal antibodies (mAbs) directed against the human pan-B-cell antigen CD19, a xenotransplantation model was developed in which the human Burkitt's cell line Daudi is s.c. transplanted into nude mice. IgG1, IgG2b, and IgG2a isotype variants of the anti-CD19 mAb (CLB-CD19) were tested for their capacity to inhibit the growth of 10 x 10(6) Daudi cells injected s.c. into nude mice. When mAb treatment was started 30 min after the injection of tumor cells, only the IgG2a isotype of CLB-CD19 had a marked antitumor effect in vivo. If treatment with IgG2a anti-CD19 mAb alone was delayed until Day 10 after tumor injection, no therapeutic effect was observed. However, the combination of this delayed mAb treatment with recombinant interleukin 2 (rIL-2) inhibited the growth of the Daudi cells in the nude mice, while treatment with rIL-2 alone was ineffective. The results of in vitro experiments showed that peritoneal exudate cells were able to inhibit the proliferation of Daudi cells in the presence of the IgG2a isotype variant of CLB-CD19 mAb but not in the presence of the other CLB-CD19 mAb isotype variants. Fresh nude mouse spleen cells did not mediate antibody-dependent cellular cytotoxicity against CLB-CD19 mAb-sensitized Daudi cells, irrespective of the isotype used for sensitization. However, preculture of these spleen cells with rIL-2 induced antibody-dependent cellular cytotoxicity against CD19+ target cells sensitized with CLB-CD19 mAb of all isotypes. These results indicate that it is possible to enhance mAb-dependent effector systems in vivo with the lymphokine rIL-2.

Animals↗
PubMed1989

Functional and molecular characterization of B cell line derived interleukin-1 alpha.

The cytokine secreted by a human hybrid B cell line (STS 25) obtained by fusion of the B lymphoblastoid cell line WI-L2-729-HF2 with neoplastic B cells from a patient with B cell non-Hodgkin's lymphoma (B-NHL) was characterized as IL-1 alpha. STS 25 cells express the idiotypic (Id+) immunoglobulin (Ig) specific for the neoplastic B cells of the B-NHL patient. STS 25 cells are weakly positive for surface mu delta kappa and in addition express the surface markers CD19, CD20, CD23, HLA class I and II, and the 4F2 activation antigen. STS 25 cells are also Epstein-Barr nuclear antigen positive but do not secrete viral particles. Serum-free culture supernatant from STS 25 cells (STS 25 SUP) does not show activity in assays for interleukin-2 (IL-2), -4 (IL-4), -6 (IL-6), interferon or tumor necrosis factor, but is active in the thymocyte costimulation assay and the D10.G4.1 T helper clone proliferation assay for interleukin-1 (IL-1). The IL-1 character of the STS 25 SUP activity was confirmed in inhibition studies with three different poly- or monoclonal anti-IL-1 antibodies (31, 88, and 94% inhibition in thymocyte costimulation assay, respectively). Furthermore, complete blocking of D10.G4.1 cell proliferation mediated by STS 25 SUP was observed by including anti-IL-1 alpha specific antibody in the assay, whereas anti-IL-1 beta antibody had no effect. These results indicate that this STS 25 SUP activity can be attributed to the presence of IL-1 alpha in the supernatant. Northern blot analysis of total STS 25 cellular RNA using IL-1 alpha or IL-1 beta specific probes revealed the constitutive expression of IL-1 alpha messenger RNA by STS 25 cells. In contrast, no IL-1 beta message was detectable, not even after treatment of the cells with phorbol ester or cycloheximide, which resulted in approximately 5-fold enhancement of IL-1 alpha mRNA expression. Binding studies with radiolabeled recombinant (r) IL-1 alpha indicated the presence of high numbers of IL-1 receptors on STS 25 cells (1,170 per cell, Kd = 392 pM). Although both IL-1 alpha and IL-1 beta bound to these IL-1 receptors, no indication was found for IL-1 mediated regulation of STS 25 cell growth.(ABSTRACT TRUNCATED AT 400 WORDS)

B-Lymphocytes↗
PubMed1988

Idiotypic immunoglobulin secretion by human B cell non-Hodgkin's lymphomas is related to the expression of the interleukin-2 receptor.

Tumor cells from 5 human B cell non-Hodgkin's lymphoma (B-NHL) patients were investigated for proliferative activity and idiotypic (Id+) immunoglobulin (Ig) secretion in serum-free medium without deliberate addition of B cell growth or differentiation factors (BCDF). These data were compared with cell surface marker expression, notably of activation antigens such as 4F2 and interleukin-2 (IL-2) receptor. Cells from all patients became 4F2 positive at the end of the 6-day culture period. Freshly drawn cells from 3 out of 5 patients expressed the IL-2 receptor (CD25; Tac antigen) or acquired this marker during culture in vitro and secreted relatively high levels of Id+ Ig in vitro. This correlated with elevated serum Id levels (greater than or equal to 0.5 micrograms/ml in vitro versus greater than or equal to 20 micrograms/ml in vivo). In the 2 CD25 (Tac)- B-NHL patients serum Id levels were below the detection limit and the amount of Id+ Ig secreted in vitro did not surpass 50 ng/ml. Only the B-NHL cells from a single patient were initially CD25 (Tac) positive and only these cells proliferated in serum-free culture. To test whether IL-2 receptor expression in the 3 CD25 (Tac)+ patients was functional, recombinant IL-2 (rIL-2) either alone or in conjunction with BCDF and recombinant IL-4 (rIL-4) was added to the cultures. In 2 out of 3 CD25 (Tac)+ patients rIL-2 was capable of enhancing proliferation or Ig secretion. In addition rIL-2 was found to enhance BCDF-mediated but not rIL-4 mediated responses. The third CD25 (Tac)+ B-NHL population was resistant to any of these lymphokines. Thus, this serum-free culture system may accurately reflect patient serum Id levels. IL-2 appears to regulate not only the in vitro but also the in vivo Ig secretion by neoplastic B cells.

Antigens, Surface↗
PubMed1986

Mouse monoclonal antibodies direct phagocytosis of tumor cells by human monocytes.

Human peripheral blood monocytes were found to be capable of phagocytizing human B-non Hodgkin's lymphoma (NHL) cells coated with mouse monoclonal antibodies (MoAbs). The MoAbs used recognized idiotypic determinants on the surface immunoglobulin (Ig) of the tumor cells. MoAbs of IgG1 and IgG2a subclass were equally effective in inducing phagocytosis. Preincubation of the monocytes with heat aggregated Ig from human or mouse serum inhibited phagocytosis to the same degree, suggesting involvement of an Fc receptor on the monocytes that binds both human and mouse antibodies.

Animals↗
PubMed1985

Treatment of two patients with B cell lymphoma with monoclonal anti-idiotype antibodies.

Mouse monoclonal anti-idiotype antibodies have been used to treat two patients with progressive advanced B cell non-Hodgkin's lymphoma. Transient falls in the level of circulating malignant cells and idiotypic immunoglobulin were produced, and free unbound monoclonal antibody was identified in the serum. Homing of the antibodies to tumor cells in the blood, bone marrow, ascites, and lymph nodes was demonstrated in both patients. Although large amounts of anti-idiotype antibody were given (3.8 g and 5.8 g), no toxic effects were seen, and no antibodies to the foreign mouse protein were made. There was no modulation of the antigen from the tumor cells and no indication of immunoselection. There was evidence of large-scale tumor cell destruction, but only a modest reduction in tumor size. The killing of the tumor cells was mediated by the reticuloendothelial system and not by complement.

Aged↗
PubMed1984

Dynamic studies of lymphocytes labelled with indium-111 during and after treatment with monoclonal anti-idiotype antibody in advanced B cell lymphoma.

The migration pattern of lymphocytes labelled with indium-111 was followed in a patient with B cell non-Hodgkin's lymphoma treated with a murine monoclonal anti-idiotype antibody. During the early phase of continuous infusion of antibody rapid fluxes of labelled lymphocytes into and out of the blood were seen. Dynamic scanning showed immediate uptake in the lungs; thereafter activity decreased in the lungs and increased in the liver. Studies of labelled and unlabelled cells in the circulation showed that treatment resulted in the removal of lymphocytes from the blood which was repopulated from an extravascular compartment. Tumour cells were shown to be cleared from the blood by the reticuloendothelial system in the liver. Indium-111 should be used circumspectly because it may cause chromosomal damage in labelled cells, but it is clearly useful as a radiolabel for following the migration pathways of lymphocytes in vivo.

Aged↗
PubMed1984

Mouse monoclonal antibodies against the idiotype of human B cell non-Hodgkin lymphomas: production, characterization and use to monitor the progress of disease.

Four monoclonal anti-idiotype (Id) antibodies against B cell non-Hodgkin lymphomas have been made by a simple and rapid procedure for hybridoma production that does not use isolated Id-carrying immunoglobulin. Mice were immunized with plasma membranes from the tumor cells. Screening of hybridoma colonies using an autologous T cell line and a cell line bearing the same immunoglobulins as the malignant lymphocytes as well as the capping phenomenon on the patient's own tumor cells, allowed selection of hybridomas producing anti-Id antibodies. These anti-Id antibodies were used to demonstrate variations in the circulating malignant cell population and fluctuations in the level of circulating free Id.

Animals↗
PubMed1983

Characterization of monoclonal antibodies against cell surface molecules associated with cytotoxic activity of natural and activated killer cells and cloned CTL lines.

Supernatants of hybridomas from fused spleen cells of mice immunized with either a T4+ or a T8+ CTL clone, were screened for their ability to inhibit the cytotoxic activity of the T4+ and the T8+ CTL clone. Eight monoclonal antibodies (MAbs) with blocking activity were obtained and a preliminary characterization of these antibodies was carried out. The MAbs SPV-L1 and SPV-L5 were found to react with thymocytes and all peripheral blood leukocytes. SPV-L1 and SPV-L5 precipitated a molecular complex consisting of two noncovalently bound chains of molecular weights of 95 and 160 kD indicating that they recognize the human equivalents of the recently described leukocyte function associated (LFA-1) antigens. The SPV-L1 and SPV-L5 antibodies inhibited the reactivity of six CTL clones tested in this study. In addition, SPV-L1 and L5 blocked the lectin dependent cellular cytotoxicity mediated by these CTL clones. Natural killer cell activity mediated by fresh peripheral blood lymphocytes and activated killer cell activity generated in MLC both measured against K562 was also inhibited by SPV-L1 and SPV-L5. Two other antibodies, SPV-L3 and SPV-L4 blocked strongly the cytotoxic activity of two T4+ CTL clones, whereas the reactivity of the three T8+ CTL clones and one T4+ CTL clone was not or only moderately inhibited. These antibodies recognized an Ia antigen as judged from tissue distribution and immunoprecipitation studies. However, these latter studies also suggest that SPV-L3 and SPV-L4 recognize HLA-DC rather than HLA-DR antigens. Finally, three antibodies (SPV-T3a, SPV-T3b, SPV-T3c) were obtained directed against the T3 molecular complex and one MAb (SPV-T8) was found to react with T8. The anti-T3 reagents were shown to be mitogenic for peripheral blood lymphocytes, with the exception of SPV-T3a. The results presented here indicate that the antigens recognized by SPV-L1 and SPV-L5 are involved in various cytotoxic reactions. In contrast, SPV-L3, SPV-T3 and SPV-T8 only seem to play a role in antigen specific cytotoxic reactions.

Animals↗
PubMed1975

Increased expression of a normal lymphocyte membrane antigen on chronic lymphatic leukemia cells.

Rabbit antisera against a 3 M KCl extract from lymphocytes isolated from tonsils were found to detect an antigen of the normal lymphocyte membrane that on chronic lymphatic leukemia cells is increased in quantity. This increase seems to be specific for chronic lymphatic leukemia. A discrepancy was found between the results obtained with complement-dependent techniques and with methods wherein no complement is used. In complement-dependent methods, the antisera showed a much weaker reaction with normal lymphocytes than would be expected from the amount of antigen present, as established by other methods.

Antigens↗
PubMed1971

Association of lactoferrin with other proteins, as demonstrated by changes in electrophoretic mobility.

Lactoferrin in a number of human body fluids was found to possess different electrophoretic mobilities, while being immunologically identical. The isolated protein migrated slower than any of the naturally occurring forms. This phenomenon was found to be due to the property of human lactoferrin to interact strongly with acidic macromolecules, forming complexes with a faster migration than the single protein. Beside electrostatic interactions also other forces seem to be involved in the complex formation.

Apoproteins↗