The in vivo anti-tumor activity of immunotoxins containing two versus one deglycosylated ricin A chains.
We have compared the in vitro and in vivo activities of three deglycosylated ricin A chain (dgA)-containing immunotoxins (ITs) with one versus two molecules of dgA per molecule of IgG. Two of the ITs (anti-CD19-dgA2 and anti-CD25-dgA2) had 3-0-fold improvements over their dgA1 counterparts in vitro. However, the in vivo anti-tumor activity of both constructs of each IT was the same. In contrast, anti-CD22-dgA2 was 7-fold more potent in vitro and significantly more potent in vivo than its dgA1 counterpart. These studies suggest that monoclonal antibodies must be individually tested to determine whether the addition of two versus one dgA will improve cytotoxic activity in vivo.
Cancer Immunobiology Center, University of Texas Southwestern Medical Center, Dallas 75235-8576, USA.
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Schnell
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000937:Antigen-Antibody Reactions; D015703:Antigens, CD / Q000276:immunology; D018941:Antigens, CD19 / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D002051:Burkitt Lymphoma / Q000188:drug therapy; D015815:Cell Adhesion Molecules; D003602:Cytotoxicity, Immunologic; D005260:Female; D006031:Glycosylation; D006689:Hodgkin Disease / Q000188:drug therapy; D006801:Humans; D000922:Immunotoxins / Q000737:chemistry* / Q000627:therapeutic use*; D037102:Lectins; D008223:Lymphoma / Q000188:drug therapy*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D015375:Receptors, Interleukin-2 / Q000276:immunology; D012276:Ricin / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D051918:Sialic Acid Binding Ig-like Lectin 2; D014407:Tumor Cells, Cultured / Q000637:transplantation
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D000972:Antineoplastic Agents, Phytogenic; C497867:CD22 protein, human; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D000922:Immunotoxins; D037102:Lectins; D015375:Receptors, Interleukin-2; D051918:Sialic Acid Binding Ig-like Lectin 2; D012276:Ricin