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  • 1
    Electronic Resource
    Electronic Resource
    Monoclonal antibody therapies–a ‘constant’ threat to cancer (2000)
    [s.l.] : Nature America Inc.
    Nature medicine 6 (2000), S. 373-374 
    Details
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The technology to create monoclonal antibodies was first described 25 years ago. Shortly after their discovery, monoclonal antibodies were used for the treatment of cancer, but only recently have clinical results confirmed their efficacy. The successes of cancer therapies involving monoclonal ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/74621
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    IgM monoclonal antibody JD118 recognizes an inducible antigen target for human-complement-mediated cytotoxicity against neoplastic B cells (1993)
    Springer
    Cancer immunology immunotherapy 36 (1993), S. 387-396 
    Details
    ISSN: 1432-0851
    Keywords: Monoclonal antibodies ; B cell neoplasms ; Complement-dependent cytotoxicity ; IgM ; Antigen upregulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Cancer therapy using unconjugated monoclonal antibodies (mAb) has been limited by the lack of immune effector function of the mAb and antigenic modulation. JD118 is a cytotoxic murine IgM mAb with reactivity restricted to a subset of normal B cells, some monocytic series cells, and a large percentage of B cell hematopoietic neoplasms including acute and chronic leukemias and lymphomas. Specificity was determined on several hundred normal and neoplastic, hematopoietic and non-hematopoietic cells and tissues, as well as progenitor cells. JD118 was able to kill fresh human leukemias and lymphomas in the presence of human serum as a complement source with an LD50 of 100 ng/ml. At this mAb concentration, fewer than 4% of more than 105 available target sites were bound. Killing was not affected by changes in antigen expression observed during the cell cycle nor by loss of cell-surface targets via antigenic modulation. Cytotoxicity could be achieved with human serum diluted as low as 5%, suggesting that complement depletion in vivo should not limit activity. Autologous human serum could be used effectively as a complement source. The JD118 antigen target has not been identified, but it appears to be a glycoprotein. Up-regulation of antigen expression on normal B cells and chronic lymphocytic leukemia cells in vitro resulted in antigen-negative neoplasms becoming positive and thus targets for JD118 killing. The restricted expression, potent cytotoxic characteristics, and potential for up-regulation of its antigen make JD118 a possible candidate for ex vivo autologous bone marrow purging and in vivo therapeutic trials in patients with B cell neoplasms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01742255
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Characterization of murine and humanized anti-CD33, gelonin immunotoxins reactive against myeloid leukemias (1994)
    Springer
    Cancer immunology immunotherapy 39 (1994), S. 367-374 
    Details
    ISSN: 1432-0851
    Keywords: Myeloid leukemia ; CD33 ; Immunotoxin ; Gelonin ; M195 ; HuM195
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract M195 antibodies recognize CD33, an antigen present on acute myeloid leukemia blasts as well as some myeloid progenitor cells, but not on the ultimate hematopoietic progenitor stem cell. Immunotoxins (IT) reactive with human myeloid leukemias were constructed by conjugating gelonin, a single-chain ribosome-inactivating protein, to murine and genetically engineered, humanized M195 antibodies via anN-succinimidyl-3-(2-pyridyldithio)-propionate linkage. No losses of gelonin cytotoxic activity or M195 binding activity were observed after conjugation of up to two toxin molecules per antibody. Toxin conjugates displayed specific, potent toxicity for CD33+ cells. The murine and humanized IT were not toxic to CD33− cells and were 600 and 4500 times more potent, respectively, than free gelonin in inhibiting CD33+ HL60 cells. Treatment of HL60 cells with 1 μg/ml HuM195-gelonin resulted in more than 1000 times lower colony formation; normal bone marrow mononuclear cell colonyforming units treated with HuM195-IT were reduced by a factor of 10. HL60 leukemia cells could be effectively purged from an excess of normal bone marrow cells. Exposure of target cells to IT for as little as 30 min was as effective as continuous exposure of IT for up to 6 days. However, measures of the efficacy of the immunotoxin were directly related to the length of time of observation after IT exposure and were inversely related to cell concentration. M195-gelonin immunoconjugates are potential candidates for therapeutic use in in vivo or ex vivo bone marrow purging of myeloid leukemias.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01534423
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Radioimmunotherapy with alpha-emitting nuclides (1998)
    Springer
    European journal of nuclear medicine 25 (1998), S. 1341-1351 
    Details
    ISSN: 1619-7089
    Keywords: Key words: High linear energy transfer ; Bismuth-213 ; Astatine-211 ; Bismuth-212 ; Actinium-225 ; Alpha particle-emitting radionuclides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. This review discusses the application of alpha particle-emitting radionuclides in targeted radioimmunotherapy. It will outline the production and chemistry of astatine-211, bismuth-212, lead-212, actinium-225, bismuth-213, fermium-255, radium-223 and terbium-149, which at present are the most promising alpha-emitting isotopes available for human clinical use. The selective cytotoxicity offered by alpha particle-emitting radioimmunoconstructs is due to the high linear energy transfer and short particle path length of these radionuclides. Based upon the pharmacokinetics of alpha particle-emitting radioimmunoconstructs, both stochastic and conventional dosimetric methodology is discussed, as is the preclinical and initial clinical use of these radionuclides conjugated to monoclonal antibodies for the treatment of human neoplasia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002590050306
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    Paper (German National Licenses)
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