Biomaterial Database

The effect of antibody valency and lysosomotropic amines on the synergy between ricin A chain- and ricin B chain-containing immunotoxins. 1986

R J Fulton, and J W Uhr, and E S Vitetta

The cytotoxicity of A chain immunotoxins containing IgG or Fab fragments specific for the surface immunoglobulin of the Daudi cell line was assessed in the presence of B chain immunotoxins (IgG or Fab) or lysosomotropic amines, or both. The concentration required for 50% inhibition of protein synthesis (IC50) in Daudi cells was 1.3 X 10(-8) M for IgG-A and 5 X 10(-8) M for Fab-A. The toxicity of both A chain immunotoxins was enhanced twofold by ammonium chloride. In the presence of A chain immunotoxins and ammonium chloride, a maximum of 99 and 90% reduction of clonal precursors was obtained with IgG and Fab-A chain immunotoxins respectively. Immunotoxins containing ricin B chain and IgG or Fab fragments specific for the antibody portion of A chain immunotoxins were used as secondary "piggyback" immunotoxins to treat cells that were pretreated with A chain immunotoxins. Both B chain immunotoxins were nontoxic at 1 X 10(-6) M. When added to target cells pretreated with specific A chain immunotoxins, the IC50 of the A chain immunotoxins was decreased up to 16-fold in the absence of ammonium chloride. In contrast to the results obtained with A chain immunotoxins alone, ammonium chloride significantly increased the toxicity of the complete piggyback system, resulting in the killing of 99.999% or five logs of target cells in the clonal assay. This decreased the IC50 of A chain immunotoxins up to 116-fold when compared with A chain immunotoxin alone. This enhanced toxicity was independent of the valency of either immunotoxin.

UI	MeSH Term	Description	Entries
D007074	Immunoglobulin G	The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.	Gamma Globulin, 7S,IgG,IgG Antibody,Allerglobuline,IgG(T),IgG1,IgG2,IgG2A,IgG2B,IgG3,IgG4,Immunoglobulin GT,Polyglobin,7S Gamma Globulin,Antibody, IgG,GT, Immunoglobulin
D007140	Immunoglobulin Fab Fragments	Univalent antigen-binding fragments composed of one entire IMMUNOGLOBULIN LIGHT CHAIN and the amino terminal end of one of the IMMUNOGLOBULIN HEAVY CHAINS from the hinge region, linked to each other by disulfide bonds. Fab contains the IMMUNOGLOBULIN VARIABLE REGIONS, which are part of the antigen-binding site, and the first IMMUNOGLOBULIN CONSTANT REGIONS. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme PAPAIN.	Fab Fragment,Fab Fragments,Ig Fab Fragments,Immunoglobulins, Fab Fragment,Fab Immunoglobulin Fragments,Immunoglobulin Fab Fragment,Immunoglobulins, Fab,Fab Fragment Immunoglobulins,Fab Fragment, Immunoglobulin,Fab Fragments, Immunoglobulin,Fragment Immunoglobulins, Fab,Fragment, Fab,Immunoglobulin Fragments, Fab
D008247	Lysosomes	A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes MEMBRANE FUSION. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed).	Autolysosome,Autolysosomes,Lysosome
D008807	Mice, Inbred BALB C	An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research.	BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D002051	Burkitt Lymphoma	A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.	African Lymphoma,Burkitt Cell Leukemia,Burkitt Tumor,Lymphoma, Burkitt,Burkitt Leukemia,Burkitt's Leukemia,Burkitt's Lymphoma,Burkitt's Tumor,Leukemia, Lymphoblastic, Burkitt-Type,Leukemia, Lymphocytic, L3,Lymphocytic Leukemia, L3,Burkitts Leukemia,Burkitts Lymphoma,Burkitts Tumor,L3 Lymphocytic Leukemia,L3 Lymphocytic Leukemias,Leukemia, Burkitt,Leukemia, Burkitt Cell,Leukemia, Burkitt's,Leukemia, L3 Lymphocytic,Lymphoma, African,Lymphoma, Burkitt's,Tumor, Burkitt,Tumor, Burkitt's
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D002999	Clone Cells	A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)	Clones,Cell, Clone,Cells, Clone,Clone,Clone Cell
D003602	Cytotoxicity, Immunologic	The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.	Tumoricidal Activity, Immunologic,Immunologic Cytotoxicity,Immunologic Tumoricidal Activities,Immunologic Tumoricidal Activity,Tumoricidal Activities, Immunologic
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man