Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is known that anti-alpha(1 --> 3) dextran antibodies of BALB/c mice are ordinarily of distinctive idiotypes (Id), one of which is the individual idiotype (IdI) that is represented by J558 or M104E to myeloma protein. In the present study, we established T cell line of Th1 type which recognized the Id of anti-alpha(1 --> 3) dextran antibody, and investigated its specificity and functions. The T cell line, named J-2R, had a phenotype of CD3+ CD4+ CD8- and expressed alphabeta-T cell receptors (TcR). J-2R proliferated in response to J558 in an I-Ed-restricted manner but did not respond to M104E which had substitution at amino acids 100 and 101. We confirmed that J-2R recognized J558 IdI, using synthetic peptides corresponding to two serial amino acid residues, Arg100 and Tyr101, spanning the J558 IdI in the third hypervariable region (hv3) of the heavy chain. alpha(1 --> 3) dextran-binding B cells which were isolated from dextran-immunized mice activated J-2R, but B cells from nonimmune mice did not. J-2R produced IL-2, IFN-gamma and IL-6, but did not produce IL-4, IL-5, or IL-10. Furthermore, J-2R inhibited the growth of J558 myeloma cells inoculated to the syngeneic mice in vivo. These findings suggest that Id-specific CD4+ T cells, J-2R, are involved in Id network and may play a role in vivo. J-2R is useful for analysis of the role of the Id-specific helper T cells in immune network because J558 IdI is frequently present on anti-alpha(1 --> 3) dextran antibodies.
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PMID:Establishment and characterization of an anti-idiotypic CD4+ CD8- T cell line to murine anti-alpha(1 --> 3) dextran antibody. 895 18

Neopterin, a pteridine derivate, is produced and released by lymphocytes and monocytes/macrophages after stimulation by T-cell derived interferon (IFN) gamma. The urinary excretion of neopterin and plasma IFN-gamma levels were measured in 35 patients with multiple myeloma (MM) and 21 patients with other monoclonal gammapathies (MG). Significantly higher excretion of neopterin was found in patients with MM in the time of diagnosis and/or progressive phase of disease (median 963,7 mumol/mol creatinine, range 183,9-2 376,3) comparing the patients in stable phase of MM (median 407,4, range 184,3-826,4), monoclonal gammapathy of undetermined significance (406,2, 226,9-1 689,3) and other MG (452,5, 240, 4-913,6) (p < 0,05). Elevation of urinary neopterin levels preceded changes of other parameters of disease activity by several months, persistent high urinary excretion was associated with refractory disease respectively. The differences of neopterin levels between patients of various clinical stages of MM was observed in newly diagnosed and progressive disease (III. vs. I and II. clinical stage, p < 0.05), but not in stable phase of MM. The plasma concentration of IFN-gama were insignificantly higher in MM than in health controls, however, the difference between all groups of patients was not found. We conclude, that neopterin is a good marker of disease activity in patients with MM. The plasma levels of its regulatory cytokine, IFN-gama, did not correlate with urine neopterin levels in our study.
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PMID:[Urinary excretion of neopterin and plasma levels of interferon gamma in patients with multiple myeloma]. 897 55

Tumour-specific CD4+ T helper (Th) and CD8+ T cytotoxic (Tc) cells may participate in the control and eradication of tumour cells. In the present study, idiotype-specific stimulation of CD4+ and CD8+ blood T cells from patients with monoclonal gammopathy of undetermined significance and patients with untreated multiple myeloma stage I was examined. Activation was measured in the CD4+ and CD8+ subsets enriched by magnetic microbeads as the incorporation of 3H-thymidine and the secretion of interferon (IFN)-gamma, interleukin (IL)-2 and IL-4 by single cells using the enzyme-linked immunospot assay. Idiotype-specific T cells were found in four of seven patients. Stimulation was mainly confined to the CD4+ subset in three of the four responding patients. This type of response was major histocompatibility complex (MHC) class II restricted as it could be inhibited by monoclonal antibodies against MHC class II (HLA-DR), but not against class I (HLA-ABC) molecules. Idiotype-specific CD8+ T cells were also demonstrated in these patients although at a lower frequency. One patient showed a strong and dominating activation of CD8+ T cells which could be blocked by antibodies against HLA-ABC but not against HLA-DR. Idiotype-specific CD4+ or CD8+ T cells were mainly of the type-1 subsets as judged by their secretion of IFN-gamma and IL-2. Thus, this study provides evidence for the presence of idiotype-specific and MHC-restricted CD4+ and CD8+ T cells of the type-1 subsets in patients with monoclonal gammopathies. Such T cells with the potential to control the growth of tumour B cells may be a suitable target for immunotherapeutic interventions in patients.
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PMID:Idiotype-specific T lymphocytes in monoclonal gammopathies: evidence for the presence of CD4+ and CD8+ subsets. 902 23

Gene transfer of the costimulatory molecules B7-1 and B7-2 induces a potent antitumor immune response in a variety of tumor models. B cell neoplasms including multiple myeloma (MM) often show little or no expression of B7 antigens; they are therefore a potential target for this approach. To increase the expression of human B7 genes in MM cells, both genes and the neomycin phosphotransferase gene were packaged into recombinant adeno-associated virus vectors (rAAV). The resulting recombinant viruses rAAV/B7-1, rAAV/B7-2 and rAAV/Neo were used to transduce the MM cell lines LP-1 and RPMI 8226. This allowed the transduction of up to 80% of LP-1 cells 4 days after infection with purified rAAV particles. The response of human allogeneic T cells to rAAV/B7-1 and rAAV/B7-2 transduced, gamma-irradiated LP-1 cells was assessed by [3H]thymidine incorporation, by RT-PCR-based detection of immunostimulatory cytokine transcripts and by ELISA quantification of cytokines in the supernatant. Stimulation of T cells with rAAV/B7-1 or rAAV/B7-2 transduced LP-1 cells resulted in an up to 10-fold increase of T cell proliferation when compared with LP-1 cells transduced with rAAV/Neo. Similar results were obtained with RPMI 8226 cells. Both rAAV/B7-1 and rAAV/B7-2 transduced LP-1 cells stimulated the T cell secretion of IL-2 and IFN-gamma. Furthermore, [51Cr] release assays showed that rAAV/B7-1 or rAAV/B7-2 transduced LP-1 cells induced a cytolytic T cell (CTL) response, in contrast to LP-1 cells transduced with rAAV/Neo. In all assays, the effects of rAAV/B7-1 and rAAV/B7-2 were similar. Taken together, the results show that rAAV-mediated transfer of B7 genes into MM cell lines is able to enhance the antitumor T cell response and to elicit a cytolytic T cell response.
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PMID:Gene transfer of the costimulatory molecules B7-1 and B7-2 into human multiple myeloma cells by recombinant adeno-associated virus enhances the cytolytic T cell response. 928 74

Interleukin-18 (IL-18)/interferon-gamma-inducing factor (IGIF) is a novel cytokine, which is a potent inducer of IFN-gamma production and plays an important role in Th1 responses. In order to develop a specific ELISA for the measurement of human IL-18, we established 13 anti-human IL-18 monoclonal antibodies and characterized them. 7 murine anti-human IL-18 mAbs and 6 rat anti-human IL-18 mAbs were obtained by fusion of splenocytes from mice or rats immunized with human IL-18, with SP2/0 myeloma cells. These antibodies were classified into 4 groups according to competitive binding ELISAs to the human IL-18 molecule. 1 murine mAb and all 6 rat mAbs neutralized IFN-gamma production induced by IL-18. A specific human IL-18 ELISA was developed using two neutralizing mAbs (#125-2H and #159-12B). This ELISA detects human IL-18 with a minimum detection limit of 10 pg/ml, but does not react with heat-denatured human IL-18. The ELISA does not show any cross-reactivity with other cytokines. Using this assay, human IL-18 was measurable in the plasma of leukemia patients. This ELISA would become a powerful tool for investigating the relationship between IL-18 and various diseases or analyzing the control mechanisms of IL-18 production from IL-18 producing cells.
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PMID:Characterization of anti-human interleukin-18 (IL-18)/interferon-gamma-inducing factor (IGIF) monoclonal antibodies and their application in the measurement of human IL-18 by ELISA. 932 73

IFN-gamma is a cytokine which functions in a wide range of biological activities by inducing a number of early and delayed genes. In murine IL-3-dependent cell lines BAF-B03 and 32D, IFN-gamma upregulated bag-1 and bcl-xL gene expression. These cells revealed prolonged cell survival against IL-3-deprivation by IFN-gamma stimulation. In contrast, human myeloma cell line RPMI8226, despite expression of IFN-gamma receptor, showed neither induction of their expressions nor prolonged cell survival against serum starvation-induced apoptosis by IFN-gamma stimulation. Gene-transfer-mediated overexpression of BAG-1 protein in BAF-B03 cells led to prolonged cell survival against IL-3-deprived apoptosis compared with control BAF-B03 transfectants, indicating that levels of BAG-1 expression are crucial for cell survival in BAF-B03 cells. Taken together, these studies suggest that induction of anti-apoptotic gene expression is a crucial factor for the anti-apoptotic function of IFN-gamma in IL-3-dependent immature hematopoietic cells.
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PMID:IFN-gamma upregulates anti-apoptotic gene expression and inhibits apoptosis in IL-3-dependent hematopoietic cells. 934 41

The monoclonal immunoglobulin (Ig) (M-component) secreted by the tumour plasma cells in multiple myeloma (MM) has specific antigenic determinants (idiotypes; id) that can serve as tumour-specific antigens. The intact Ig molecule is a weak antigen, and small fragments of id protein might be more immunogenic for the induction of id-specific immunity. Dendritic cells (DC) have attracted attention as the most efficient antigen-presenting cells and promising adjuvants for immunotherapy in tumours. In this study the in vitro T-cell response against F(ab')2 and Fab fragments, heavy and light chains of the M-component was examined in five patients with MM clinical stage I. All fragments were able to stimulate T cells but F(ab')2 or Fab fragments and heavy chains induced a stronger response than light chains. DC induced a significantly stronger id-specific immune response than monocytes. Moreover, with DC as antigen-presenting cells, a predominant interferon (IFN)-gamma (type-1 T-cell) response was seen in all patients. Both IFN-gamma and interleukin (IL)-4 (type-1 and type-2 T-cell) responses were noted when monocytes were used. Our study suggests that DC pulsed with idiotypic fragments such as F(ab')2 fragment and heavy chain can be used for the induction of type-1 anti-idiotypic T-cell response for immunotherapy in MM.
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PMID:Anti-idiotypic T-cell activation in multiple myeloma induced by M-component fragments presented by dendritic cells. 953 29

This study was designed to investigate the effect of 1.8 x 10(6) U/day interleukin 2 (IL-2) therapy on interferon (IFN) production. Patients enrolled in the study suffered from multiple myeloma (MM), Hodgkin's disease (HD) and non-Hodgkin lymphoma (NHL). All of them were in remission after chemotherapy or radiotherapy. Results indicated that IL-2 given subcutaneously at a dose of 1.8 x 10(6) U/day for 3 weeks induced IFN-gamma in serum of patients and caused a prolonged effect on the ability of blood leukocytes to produce IFN-gamma after stimulation in vitro by mitogen phytohemagglutinin (PHA). Such enhancement of IFN-gamma production may be beneficial for antitumor immune response. Low-dose IL-2 therapy was well tolerated by all patients and side effects not exceeding II grade of toxicity according to WHO scale were observed. Five patients with MM have relapsed 3-10 months after cesation of IL-2 therapy but 15 patients 18 months after therapy were in complete remission.
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PMID:Modulating effect of interleukin 2 therapy on interferon production by blood leukocytes of patients with minimal residual hematological disease. 959 84

Interleukin-6 (IL-6) is the major growth factor for the malignant plasma cell clone in patients with multiple myeloma (MM). Although interferon-alpha (IFN-alpha) has been widely used as maintenance therapy in MM, controversy exists as to its clinical utility. This review summarizes data showing that cell growth arrest brought about by type I (IFNs-alpha/beta) and type II (IFN-gamma) IFNs occurs in part through utilization/modification of various components of the otherwise stimulatory Jak-STAT and Ras signaling pathways triggered by IL-6. Recent experimental results indicating that IFN-alpha acts as a survival factor for certain myeloma cell lines and frequently induces endogenous IL-6 expression may help to explain the conflicting clinical findings obtained in this heterogeneous disease with this usually potent growth inhibitor. By comparison, consistent antiproliferative activity exhibited by IFN-gamma on IL-6-dependent myeloma cell lines and primary myeloma cells from patients suggests that further investigation of the possible value of this cytokine in the treatment of MM may be warranted.
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PMID:Growth control mechanisms in multiple myeloma. 964 60

Vaccination of mouse myeloma V(K)C(K)-gamma (I) cells secreting interferon (IFN)-gamma and expressing enhanced major histocompatibility complex (MHC) class I antigen (Ag) resulted in protective immunity that was mainly mediated by CD8+ T cells. V(K)C(K)-gamma (I/II) cells expressing both enhanced MHC class I and class II Ags were isolated from V(K)C(K)-gamma (I) cells. These V(K)C(K)-gamma (I/II) cells were used to study the relationship between IFN-gamma secretion of tumor cells, its tumorigenicity, and its induced immunity, as well as to evaluate the cellular immunocomponents mediating this immunity. Our animal studies showed that IFN-gamma secretion by V(K)C(K)-gamma (I/II) cells curtailed its tumorigenicity in syngeneic BALB/c mice and further induced protective immunity against a subsequent graft of parental V(K)C(K) tumor. This immunity is mediated by both CD4+ and CD8+ T cells. The activation of CD4+ T cells is associated with enhanced expression of MHC class II Ag of V(K)C(K)-gamma (I/II) cells. These CD4+ T cells are tumor specific and cytolytic in an MHC-restricted fashion in vitro, and are tumoricidal in a T-cell adoptive transfer experiment in vivo. Our data thus demonstrate that vaccination of genetically modified tumor cells secreting IFN-gamma may provide beneficial antitumor effects by inducing both cytolytic CD4+ and CD8+ cytotoxic T lymphocytes, provided that these tumor cells express both enhanced MHC class I and class II Ags.
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PMID:Cytotoxic CD4+ T cells associated with the expression of major histocompatibility complex class II antigen of mouse myeloma cells secreting interferon-gamma are cytolytic in vitro and tumoricidal in vivo. 982 51


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