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  • 1
    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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  • 2
    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
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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