PubMed · 1980 · 416 citations · 18 references
Life SciencesImmunologyOncologyCancer ImmunologyMonoclonal AntibodiesTumor ImmunologyCirculating Tumor CellsMonoclonal Antibody TherapyPharmacokinetics Of Monoclonal AntibodiesTherapeutic Monoclonal AntibodiesTumor AntigensTumor-associated AntigensAdministration Of Monoclonal AntibodiesAntibody-dependent Cell-mediated CytotoxicityAntibody-dependent Cellular CytotoxicityClinical Toxicity AssessmentComplement-mediated Cell LysisMonoclonal Antibody InfusionMonoclonal Antibody TherapeuticsTherapeutic Efficacy Assessment
A preliminary serotherapeutic trial was undertaken with a monoclonal antibody designated antibody 89 (Ab 89) directed against a lymphoma-associated antigen. In vitro studies demonstrated that Ab 89 could mediate complement-dependent lysis and macrophage adherence but not antibody-dependent cell-mediated cytotoxicity. To evaluate toxicity and therapeutic efficacy, two courses of Ab 89 were administered to a patient with an Ab 89-reactive tumor. Transient decreases in the number of circulating tumor cells and the appearance of circulating dead cells were noted with the infusion of Ab 89. Following administration of 150 mg or more of Ab 89, small amounts of antibody could be demonstrated on circulating tumor cells at a time when no free antibody was found in the serum. The inability to deliver a significant amount of Ab 89 to tumor cells in vivo is thought to be secondary to a circulating tumor antigen. Following each infusion, the amount of this blocking antigen decreased but could not be entirely cleared from the serum. This study provides preliminary evidence for the lack of clinical toxicity of a monoclonal antibody and identifies circulating blocking antigens as a significant obstacle to serotherapy.
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Continuous cultures of fused cells secreting antibody of predefined specificity
Georges Köhler, César Milstein · Nature · 1975 · 17.2K citations
Pharmacy, Cell Biology, Immunology +11