Myeloma tumor

In 1975, Kohler and Milstein observed that if an antibody-producing cell was fused with a myeloma tumor cell, a rapidly dividing hybrid was produced that synthesized a monospecific antibody. Each hybridoma formed then became a factory, producing antibodies monospecific to a particular sensitizing antigenic epitope. Cell cloning allows selection of hybrids producing antibodies with the desired characteristics. 

Kohler and Milstein are responsible for the third significant development during this time. In 1975 they demonstrated that cells derived from mouse B lymphocytes, which secrete antibodies, were fused with mouse myeloma tumor cells from a mouse, which can grow indefinitely in culture (see Fig. 3). The resulting fused cell, is a hybrid-myeloma or hybridoma cell that can grow in cell culture and produce large quantities of chemically... 

One of Tobe s complexes, cis-dichlorobis(cyclohexylamine)plati-num(II) was tested by T. A. Connors against the ADJ/PC6 myeloma tumor in mice. It cured the tumors completely at a dose 1/500 of the LD50. Such specificity, especially in the absence of any evidence of selective tumor up-... 

Munguia A, Ota T, Miest T, et al. Cell carriers to deliver oncolytic viruses to sites of myeloma tumor growth. Gene Ther 2008 15 797-806. 

Antigen-specific antibodies produced by B-cells are secreted and appear in the blood serum of an immunized animal, from where they can be isolated as polyclonal mixtures, usually from rabbits. Alternatively, isolation of B-cells from the spleen of an immunized mouse and fusion with myeloma (tumor cells) yields hybridoma , which are antibody-producing cells that can be propagated in vitro [4]. Each hybridoma cell line secreting an antigen-specific antibody can be isolated and provides a source of a single monoclonal antibody. Polyclonal and monoclonal antibodies to a variety of proteins are commercially available, and many industrial and academic laboratories offer to produce polyclonal or monoclonal antibodies. 

PI-88 Multiple myeloma. Tumor angiogenesis Progen, Medigen Phase II... 

Evens AM, Prachand S, Shi B, Paniaqua M, Gordon LI, Gartenhaus RB. Imexon-induced apoptosis in multiple myeloma tumor cells is caspase-8-dependent. Clin Cancer Res 2004 10(4) 1481-91. 

J chain is synthesized by the same cells that produce the immunoglobulin to which it is attached (188,189). It is linked to IgM or to polymeric IgA shortly before secretion from a lymphoid cell. In the case of a myeloma tumor secreting both monomeric and dimeric IgA, the amount of dimer produced appears to be a function of the quantity of J chain available (189,190). 

In 1975, the first successful production of MAbs was reported (44). By fusing normal antibody-producing cells with a B-ceU tumor (myeloma), hybridoma cell lines resulted which produced antibodies having a specificity to only one deterrninant on an antigen ie, all the antibodies produced from the cell line are identical. These studies resulted in a standard approach to MAb production. In this approach, the hybridoma cells are produced in large quantities in culture and screened to select specific clones producing the desired MAb using an appropriate assay. The selected clones are then expanded in culture (or in animals), the cells are collected, and the MAbs are extracted and purified. 

Carmustine is a bicyclohexylnitrosourea (BCNU, Fig. 3) with broad spectrum of antineoplastic activity (e.g., lymphomas, multiple myeloma, sarcomas, brain tumors, gastrointestinal tumors, melanomas). At doses of 80-200 mg/m2 it is given i.v. at 6 week s intervals. 

Bendamustine is a useful antineoplastic drug for the treatment of non-Hodgkin s lymphomas, multiple myeloma and as a partner drug in the combination therapy of some solid tumors. The cross-resistance with other alkylating drugs is not complete. Myelosuppression and lymphocytopenia is its main dose-limiting toxicity. 

Liposomal encapsulation of DOX or DNR Preferred anthracycline delivery to the tumor Breast cancer, ovarian cancer, AIDS-related Kaposi s sarcoma, multiple myeloma (pegylated liposomal DOX). Breast cancer (uncoated liposomal DOX). AIDS-related Kaposi s sarcoma, acute mye-loblastic leukemia, multiple myeloma, non-Hodgkin s lymphomas (uncoated liposomal DNR)... 

Antineoplastic agents that cannot be grouped under subheadings 1-9 include miltefosine which is an alkylphosphocholine that is used to treat skin metastasis of breast cancer, and crispantase which breaks down asparagine to aspartic acid and ammonia. It is active against tumor cells that lack the enzyme asparaginase, such as acute lymphoblastic leukemia cells. Side effects include irritation of the skin in the case of miltefosine and anaphylactic reactions in the case of crispantase. Another recent development is the proteasome inhibitor bortezomib which is used to treat multiple myeloma. 

Proteasomal inhibition represents a novel strategy in cancer treatment and the small molecule Bortezomid (PS-341, Velcade ) has been approved for the treatment of refractory and relapsed multiple myeloma, a proliferative disease of plasma cells. Bortezomid inhibits an active site in a proteasome subunit and remarkably shows selective cytotoxicity to cancer cells. Although the underlying mechanisms are not completely understood bortezomid apparently induces a cell stress response in these tumor cells followed by caspase-dependent apoptosis. Whether bortezomid is beneficial for the treatment of other proliferative disease is currently being tested in clinical trials. 

Vincristine (VCR, Oncovin) ALL HD NHL multiple myeloma breast cancer SCLC, KS brain tumors soft tissue sarcomas osteosarcomas neuroblastoma Wilms tumor... 

The primary goal in the treatment of multiple myeloma is to decrease tumor burden and minimize complications associated with the disease. A watch and wait approach is an option for asymptomatic patients who have no lytic lesions in the bone. Once symptoms occur, treatment is required. Chemotherapy can be used to reduce tumor burden in patients with symptomatic disease, but increasingly, immunomodula-tors such as thalidomide and dexamethasone are initial therapy. Almost all patients will become refractory to initial treatment and will require the use of salvage therapies such as bortezomib. Autologous stem cell transplantation prolongs overall survival in patients who can tolerate high-dose chemotherapy and may be the treatment of choice for many patients. 

Cancers Multiple myeloma Non-Hodgkin s lymphoma Hodgkin s disease Acute myeloid leukemia Neuroblastoma Germ cell tumors Acute myeloid leukemia Acute lymphoblastic leukemia Chronic myeloid leukemia Myelodysplastic syndrome Myeloproliferative disorders Non-Hodgkin s lymphoma Hodgkin s disease Chronic lymphocytic leukemia Multiple myeloma... 

Oyajobi BO, Franchin G, Williams PJ, et al. Dual effects of macrophage inflammatory protein-lalpha on osteolysis and tumor burden in the murine 5TGM1 model of myeloma bone disease. Blood 2003 102(1) 311—319. 

Mammalian cell suspension cultures are the preferred choice for large-scale recombinant protein production in stirred-tank bioreactors. The most widely used systems are Chinese hamster ovary (CHO) cells and the murine myeloma fines NSO and SP2/0. In half of the biological license approvals from 1996-2000, CHO cells were used for the production of monoclonal antibodies and other recombinant glycosylated proteins, including tPA (tissue plasminogen activator) and an IgGl fusion with the tumor necrosis factor (TNF) receptor, the latter marketed as Enbrel [7]. 

The combination of tyrphostins with cytotoxic drugs can be followed by immunotherapy in order to eliminate residual disease. Though such combinations have not yet been examined, the combination of AG 490 and IL-12 against IL-6 dependent multiple myeloma recently showed impressive tumor suppressive effects [54], suggesting that the general idea may indeed be correct. 

As well as NONOates, other NO donors also showed anticancer activity independently. Sodium nitroprusside (SNP), a metal-NO complex, showed cytotoxic effects on the cells of some patients with malignant lymphoma (ML), acute myelocytic leukemia (AML) or chronic myelomonocytic leukemia (CMMoL), but not with multiple myeloma [109]. SNP and cytosine arabinoside (Ara-C) did not share the drug resistance. Interestingly, SNP had no effect on lymphocytes of healthy volunteers. These results suggest that SNP has an anti-tumor effect on human hematological malignant cells. 

---