Cells myeloma

Mycotrienols Mycrox Myelography Myeloma cell Myfungar Myk Mykrox Mylanta Mylar... 

Monoclonal antibodies are derived from a single, monospecific B cell clone. Monoclonal antibodies can be obtained from hybridoma cells that result from the fusion of antibody-producing B cells with immortal cells of a myeloma cell line. 

The cell fusion mixture is transferred to a culture medium containing hypoxanthine, aminopterin and thymidine (HAT medium). Unflised myeloma cells are unable to grow as they lack HGPRT. Unflised normal spleen cells can grow but their proliferahon is limited and they eventually die out. The hybridoma cell can proliferate in the HAT medium as the normal spleen cell supplies the enzyme which enables the hybridoma to utilize extracellular hypoxanthine. 

Oba Y, Lee JW, Ehrlich LA, et al. MIP-lalpha utilizes both CCR1 and CCR5 to induce osteoclast formation and increase adhesion of myeloma cells to marrow stromal cells. Exp Hematol 2005 33(3) 272-278. 

Vande Broek I, Asosingh K, Vanderkerken K, et al. Chemokine receptor CCR2 is expressed by human multiple myeloma cells and mediates migration to bone marrow stromal cell-produced monocyte chemotactic proteins MCP-1, -2, and -3. Br J Cancer 2003 88 855-862. 

Cohen, S., Cahan, R., Ben-Dov, E., Nisnevitch, M., Zaritsky, A., and Michael, A.F. (2007) Specific targeting to murine myeloma cells of CytlAa toxin from Bacillus thuringiensis subsp. Israelensis. /. Biol. Chem. 10.1074/jbc.M703567200. 

On a more cautionary note, the EPO receptor is expressed not only by specific erythrocyte precursor cells, but also by endothelial, neural, and myeloma cells. Concern has been expressed that EPO, therefore, might actually stimulate growth of some tumour types, particularly those derived from such cells. To date, no evidence (in vitro or in vivo) has been obtained to support this hypothesis. 

Monoclonal antibody technology entails isolation of such B-lymphocytes, with subsequent fusion of these cells with transformed (myeloma) cells. Many of the resultant hybrid cells retain immortal characteristics, while producing large quantities of the monospecific antibody. These hybridoma cells can be cultured long term to effectively produce an inexhaustible supply of the monoclonal antibody of choice. 

Fusion of human lymphocytes with human lymphoblastoid cell lines is a very inefficient process. Fusion of human lymphocytes with murine myeloma cells lead to very unstable hybrids. Upon fusion, preferential loss of human genetic elements is often observed. Unfortunately, particularly common is the loss of chromosomes 2,14 and 22, which encode antibody light and heavy chain loci. The production yields of human monoclonals upon immortalization of the human B-lymphocyte (by whatever means) are also low. 

The thalidomide analogs CPS49 (30) and CPS11 (31) have been reported to inhibit PI3/AKT signaling in multiple myeloma cells via an anti-angiogenic effect. These compounds are devoid of the teratogenic properties seen with thalidomide and are currently in preclinical development [66]. Compound 30, and to a lesser extent 31, induced a dose-dependent inhibition of proliferation in several multiple myeloma cell lines and reduced phospho-AKT levels [66]. These compounds also inhibited DNA synthesis in cell lines resistant to conventionally used anti-multiple myeloma drugs (e.g. dexamethasone, anthracyclines and melphalan) in a dose-dependent manner. 

IL-6 induces terminal maturation of B cells, promotes the growth of hy-bridoma/myeloma cells and T cells, and acts upon haematopoietic progenitors in synergy with IL-1 and IL-3. It also induces the production of acute-phase proteins by liver cells. In addition to its production by neutrophils, IL-6 is also synthesised by monocytes, T and B cells, fibroblasts, cardiac myxoma cells, some bladder carcinomas, cervical cancer cells and glioblastomas. Stimulated neutrophils generate about ten times less IL-6 (on a per-cell basis) than do monocytes. 

Interleukin 1 (IL1) Human myeloma cells Cell growth... 

Reft, M.E., Adams, K., and Anderson, D.R., Comparison of recombinant chimeric immunoglobulin secreted and purified from Chinese hamster ovary (CHO) and murine SP2/0 myeloma cells, in American Chemical Society Conference Recovery of Biological Products Vll, American Chemical Society, San Diego, CA, September 25-30, 1994, p. 26. 

The next development was the production of monoclonal antibodies (MAbs) in the mid-1970s. This uses hybridoma technology, which involves the fusion of antibody-producing B cells to immortal myeloma cells. Figure 4.4 shows the preparation of MAbs using hybridoma techniques. A more detailed discussion of biopharmaceuticals production is presented in Section 10.5. 

Fuii Human Antibody Full human antibodies are the current engineered antibodies. Several techniques are used to construct these antibodies. One method is to fuse human B cells to myeloma cells. These hybridomas will produce fully human MAbs. Another method is to genetically alter mice in the laboratory to contain human antibody producing genes. In response to antigens, antibodies resembling the human antibodies are produced. 

Inpus erythematosus A chronic inflammatory disease of connective tissue, affecting the skin and internal organs, lymphoma A malignant tumor of the lymph nodes, multiple sclerosis A disease of the nervous system, myelodysplasia Abnormal or defective formation of the bone marrow. Mycoplasma Minute primitive bacteria without a rigid cell wall. Mycoplasma pneumoniae causes atypical pneumonia in humans, myeloma cells Malignant tumor cells. 

Ge, N.L., and Rudikoff, S., 2000, Expression ofPTEN in PTEN-defident multiple myeloma cells abolishes tumor growth in vivo. Oncogene 19 4091-4095. 

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