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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to establish human monoclonal antibodies to any sort of antigens efficiently, we have made following two approaches. Our first approach is to improve cell fusion frequency. By improving our previous method for production of human hybridomas, we obtained higher frequency (1/700 vs. 1/5500) compared with our previous method by adding irradiated myeloma cells to culture of fusion cells and modifying the selective medium. Our second approach is to use a SCID-hu mouse for immunization. Since the injection of human PBL can result in the stable long-term reconstitution of a human immune system in SCID mouse, we tried to immune SCID-hu mouse with KLH. In the serum of immunized SCID-hu mouse, we obtained human IgG antibodies to KLH. Additionally, we succeeded in establishing human B lymphoblastoid cell lines which produced antibodies specific to KLH. These methods will open new prospects for the detection and therapy of cancer.
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PMID:New strategies to establish human monoclonal antibodies. 130 17

Mice with the scid mutation have a defect in the V(D)J recombinase. In order to determine whether the SCID product is normally present in mature B cells that do not have the recombinase activity, scid pre-B cells were fused with myeloma cells. It was found that in the hybrid cells, a rearrangement test gene was correctly joined immediately after fusion. The same test gene was aberrantly rearranged in the scid pre-B cells. Stable hybrids between the scid pre-B and the myeloma cells had lost the expression of RAG-1 and RAG-2 genes, supporting the previous finding of an inhibitor of rearrangement in myeloma cells that acts shortly after fusion. Thus, mature B cells apparently contain the SCID product, the wild type SCID function is not competitively interfered with by products present in scid pre-B cells, and the SCID product seems not to be a target for the recombinase inhibitor.
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PMID:Fusion of a scid pre-B cells with a wild type (myeloma) B cell results in correct rearrangement of a V(D)J recombination substrate. 134 97

Using highly purified myeloma cells from patient bone marrow, we established human-murine myeloma chimeras in severe combined immunodeficiency (SCID) mice and documented secretion of monoclonal human immunoglobulins (Hulgs) in the mice for up to 299 days. Monoclonality of circulating Hulgs was found only when highly purified myeloma cells were injected intraperitoneally. In contrast, injection of unfractionated myeloma marrow led to the development of polyclonal Hulgs in the SCID mice. The criteria for myeloma engraftment included prolonged presence of monoclonal Hulgs in the sera of SCID mice and/or detection of human myeloma cells in their tissues by immunohistochemical examination. Ninety-one percent (10/11) of the fresh purified myeloma specimens engrafted in the SCID mice. Fifty-five percent (6/11) of the patient samples resulted in human B-cell grafts, and 45% (5/11) were identifiable as human myeloma chimeras. Pathologic studies showed that most human plasmacytes were located in the peritoneal cavity but metastatic infiltrates were also found in other organs in 69% of the SCID-human myeloma chimeras. This chimeric model should provide a useful tool for characterization of growth modulation and microenvironmental interactions as well as a means of testing new therapeutic approaches to multiple myeloma.
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PMID:Long-term engraftment of fresh human myeloma cells in SCID mice. 145 Apr 9

Myeloma is one of the interleukin (IL)-6-related diseases to which abnormal expression of IL-6 has been reported to be linked. We examined the in vivo inhibitory effect of anti-human IL-6 receptor (IL-6R) antibody on human myeloma cell growth in mice. SCID mice were subcutaneously inoculated with solid tumor of the myeloma cell line S6B45 in which human IL-6 was acting as an autocrine growth factor. Ten intraperitoneal administrations of 100 micrograms of the anti-human IL-6R antibody PM1 at 48-h intervals strongly inhibited the growth of S6B45 cells when the administration started 24 h after tumor inoculation. The tumor growth inhibition in vivo was also observed by administration of the anti-human IL-6 antibody MH166 using the same procedure as for PM1. The inhibitory effect of PM1 was not significant when the administration started 5 or more days after tumor inoculation. This work indicates that anti-human IL-6R antibody, as well as anti-human IL-6 antibody inhibits human myeloma growth in vivo, and provides an animal model for testing the therapeutic value of agents such as antibodies to human IL-6, IL-6R and gp130, an IL-6R-associated signal transducer, in the treatment of human myelomas.
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PMID:Anti-human interleukin-6 receptor antibody inhibits human myeloma growth in vivo. 163 1

The association between cancer and immunodeficiency is well established. In common variable immunodeficiency (CVI), a primary immunodeficiency disease characterized by low serum immunoglobulins and poor antibody production, we previously reported a total of 13 cancers in 11 individuals arising in continuously observed group of patients. Of the 13, 7 were NHL and 1 was a myeloma which progressed to lymphoma. We report here the histologic, immunologic, cytogenetic, and clinical features of these 8 NHL along with 3 new lymphomas which have appeared in this group (now 117 patients). From our studies, the lymphomas which have arisen in CVI share certain features with the lymphomas which appear in the childhood immunodeficient syndromes. Wiskott Aldrich Syndrome, Ataxia Telangiectasia, or severe combined immunodeficiency: they are similar in overall frequency (13%), are often B-cell in origin, and extranodal in location. However, unlike the lymphomas of the immunodeficient child, lymphomas in CVI may be more differentiated and secrete immunoglobulin. For CVI patients with stage I or II disease, as for non-Hodgkin lymphomas in general, the prognosis is good. In our group, NHL in CVI have appeared most often in females of the 5th to 7th decade and not in childhood. Cytogenetic studies in lymphomas show that cytogenic abnormalities, including chromosomal translocation, can be found in this group, but more studies will be needed to assess the frequency of these events.
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PMID:Non-Hodgkin lymphoma in common variable immunodeficiency. 182 73

In 1994, an estimated 12,700 new cases of multiple myeloma (MM) will be diagnosed in the USA and 9,800 patients will die from this disease. At present, a cure for MM has not been achieved with any chemotherapeutic regimen. Therefore, it is important to develop novel therapeutic approaches to treat this fatal disease. This review focuses on new concepts in the immunotherapy of MM. Thus far, interferons and anti-human interleukin (IL)-6 monoclonal anti-bodies (MAbs) have been used to treat patients with this disease. Bone marrow transplantation using autologous marrow purged with MAbs and complement, with anti-myeloma immunotoxins (ITs), or MAb-magnetic bead conjugates has been reported. Adoptive cellular therapy, in vivo with anti-CD3 and IL-2, as well as transplantation of purified autologous CD34+ peripheral blood stem cells, is now being evaluated in clinical trials. Anti-human IL-6 receptor (IL-6R) and anti-CD54 (ICAM-1) MAbs have shown promising results in the therapy of human myeloma cell lines in SCID mice, while an IL-6 antagonist protein, anti-gp130 MAbs, recombinant soluble gp130, anti-B7, anti-HLA-DR, and recombinant soluble CD16 also inhibit the growth of myeloma cell lines in vitro. These experimental therapeutic modalities hold promise for use in humans and may also provide further insights into the pathogenesis of MM.
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PMID:Immunotherapy of multiple myeloma. 754 Apr 68

It was known that malignancies of plasma cell (MPC) consists of three categories, one is multiple myeloma (MM), second is plasmacytoma, third is plasma cell leukemia. One of the aim of our review is that we listed MPC cell lines reported. It became clear from the list that the success of establishment of cell lines may expected only when trials are done concerning MM cells shown extra-medullary invasion cells from patients. In contrast, IL-6 dependent cell lines may established by chance and it may not depend on cell origin. The second aim of the article is to review the usage of cell lines of MPC. We chose 7 issues; one is the correlation between the proliferation and IL-6, second is the contribution of other cytokines to MPC lines, third is how to make human MM model in SCID mouse, fourth is the chromosomal abnormalities and oncogenesis, fifth is the contribution of fibronectin and MPC lines, sixth is the issue of osteoblast activating factor (OAF), finally, we discussed the tumour aberration of MPC lines. We expect that the accumulation of these acknowledges concerning MPC cell lines would contribute to the development of plasmacytology in the future.
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PMID:[Establishment and usage of human multiple myeloma cell line]. 769 92

Cells of an EBV-transformed human lymphoblastoid B cell line, producing antibodies directed against tetanus toxin, were fused with mouse myeloma cells (SP2/0) and with mouse-human heteromyeloma cells (SPAM-8) resulting in the formation of heterohybridoma and trioma cells, respectively. Antibody production of the three cell lines were studied under different culture conditions. All three cell lines produced antibodies in concentrations ranging from 2.6 to 6.4 micrograms ml-1 in spent medium from stationary flask cultures. Dialysis cultures of trioma and heterohybridoma cells resulted in concentrations of 36 and 20 micrograms ml-1, respectively, whereas no significant increase was obtained with the EBV-transformed cells. Trioma cells, cultured in a hollow fiber cartridge bioreactor produced antibodies in concentrations of average of 303 micrograms ml-1, whereas the EBV-transformed cells did not adapt to this system. Furthermore, trioma and heterohybridoma cells injected into the intraperitoneal cavity of SCID-mice, produced antibodies in ascites fluid in concentrations of 500 and 640 micrograms ml-1 respectively.
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PMID:Antibody production of a human EBV-transformed B cell line and its heterohybridoma and trioma cell line descendants in different culture systems. 775 84

Despite advances in conventional therapy, many lives continue to be lost to common forms of B-cell cancers, including leukemias, lymphomas and multiple myeloma. We propose a novel approach to therapy of such cancers using controlled expression of a diphtheria toxin gene (DT-A) to kill malignant cells. We have previously demonstrated selective killing of various cell types, in vitro and in vivo, by cell-specific, transcriptionally controlled expression of this gene. Organ-specific ablation in otherwise healthy transgenic mice has convincingly demonstrated the exquisite specificity achievable by this technique. In the studies now described, DT-A was delivered in vitro and in vivo using a novel gene delivery system employing DNA physically attached to the exterior of adenovirus. After demonstrating the efficacy of gene delivery to Epstein-Barr virus transformed human B-cells in vitro, in vivo work was performed using a SCID mouse model for B-cell lymphoma, in which protection against tumor was observed. The concepts of tissue-regulated toxin gene therapy, and this novel adenovirus gene delivery system are discussed.
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PMID:Gene therapy for B-cell lymphoma in a SCID mouse model using an immunoglobulin-regulated diphtheria toxin gene delivered by a novel adenovirus-polylysine conjugate. 781 62

Recent studies have suggested that ICAM-1 (CD54) is involved in the pathogenesis of human multiple myeloma. A monoclonal antihuman CD54 antibody has been generated by immunizing BALB/c mice with human myeloma cell lines. SCID mice injected with human ARH-77 myeloma cells develop disseminated myeloma which is similar in several respects to multiple myeloma in humans. The mice have monoclonal gammopathy and succumb to hind leg paralysis caused by infiltration of tumor cells into the thoracolumbar vertebrae, resulting in compression of the spinal cord. In the absence of treatment, the mean paralysis time of the SCID/ARH-77 mice is 29 days. When the SCID/ARH-77 mice received four consecutive daily i.v. injections of anti-CD54 mAb commencing 1 day after tumor inoculation, they survived for 150 days, at which time the experiment was terminated. Histopathological analyses indicated that prior to death all control SCID/ARH-77 mice had myeloma cells in the vertebrae and skull. At this time, the anti-CD54-treated mice had no evidence of tumor. High levels of human immunoglobulin were detected in the sera of control, but not treated mice. F(ab')2 fragments of the anti-CD54 antibody also had similar, albeit, slightly less antitumor activity in vivo, suggesting that antibody effector function may account for some, but not all the antitumor activity of anti-CD54. In vitro studies indicate that anti-CD54 does not inhibit homotypic adhesion, the binding of myeloma cells to murine bone marrow stromal cells, or cell proliferation. By exclusion, we propose that the CD54-mediated homing of these ARH-77 cells to certain anatomical sites is crucial for their growth in vivo.
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PMID:Anti-CD54 (ICAM-1) has antitumor activity in SCID mice with human myeloma cells. 783 32


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