scholarly journals Characterization of a Murine Monoclonal Antibody toCryptococcus neoformans Polysaccharide That Is a Candidate for Human Therapeutic Studies

1998 ◽  
Vol 42 (6) ◽  
pp. 1437-1446 ◽  
Author(s):  
Arturo Casadevall ◽  
Wendy Cleare ◽  
Marta Feldmesser ◽  
Aharona Glatman-Freedman ◽  
David L. Goldman ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Biological Properties ◽  
Murine Monoclonal Antibody ◽  
Preclinical Development ◽  
Antigen Binding Site ◽  
Therapeutic Trials ◽  
Mouse Tissues ◽  
Normal Human ◽  
Rapid Clearance ◽  
Immunohistochemical Studies

ABSTRACT The murine monoclonal antibody (MAb) 18B7 [immunoglobulin G1(κ)] is in preclinical development for treatment ofCryptococcus neoformans infections. In anticipation of its use in humans, we defined the serological and biological properties of MAb 18B7 in detail. Structural comparison to the related protective MAb 2H1 revealed conservation of the antigen binding site despite several amino acid differences. MAb 18B7 was shown by immunofluorescence and agglutination studies to bind to all four serotypes of C. neoformans, opsonize C. neoformans serotypes A and D, enhance human and mouse effector cell antifungal activity, and activate the complement pathway leading to deposition of complement component 3 (C3) on the cryptococcal capsule. Administration of MAb 18B7 to mice led to rapid clearance of serum cryptococcal antigen and deposition in the liver and spleen. Immunohistochemical studies revealed that MAb 18B7 bound to capsular glucuronoxylomannan in infected mouse tissues. No reactivity of MAb 18B7 with normal human, rat, or mouse tissues was detected. The results show that both the variable and constant regions of MAb 18B7 are biologically functional and support the use of this MAb in human therapeutic trials.

scholarly journals Monoclonal antibodies to laminin reveal the heterogeneity of basement membranes in the developing and adult mouse tissues.

1984 ◽  
Vol 98 (3) ◽  
pp. 971-979 ◽  
Author(s):  
Y J Wan ◽  
T C Wu ◽  
A E Chung ◽  
I Damjanov
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Adult Mouse ◽  
Basement Membranes ◽  
Newborn Mouse ◽  
Preimplantation Stage ◽  
Mouse Tissues ◽  
Reichert's Membrane ◽  
Anatomic Locations ◽  
Immunohistochemical Studies

Two monoclonal antibodies raised against laminin isolated from a mouse parietal yolk sac cell line were used for immunohistochemical studies of basement membranes of the mouse embryo and various fetal and adult tissues. No immunoreactivity with either of the two monoclonal antibodies could be detected in the preimplantation-stage embryos, although it has been shown that these embryos contain extracellular laminin reactive with the conventional polyclonal antilaminin antibodies. Reichert's membrane in early postimplantation stages of development reacted with the monoclonal antibody LAM-I but not with the antibody LAM-II. However, from day 8 of pregnancy onward the Reichert's membrane reacted with both antibodies. Basement membranes of the embryo proper were unreactive with both monoclonal antibodies until day 12 of pregnancy. By day 14 some basement membranes of the fetal tissues became reactive with one or both monoclonal antibodies, whereas others remained still unreactive. In the 17-d fetus and the newborn mouse most of the basement membranes reacted with both monoclonal antibodies, whereas others still reacted with only one. Similar heterogeneity in the immunoreactivity of basement membranes of various tissues was noted in the adult mouse as well. These results indicate that the immunoreactivity of laminin in the extracellular matrix changes during development and that the basement membranes in various anatomic locations display heterogeneity even in the adult mouse.

scholarly journals Characterization of the murine 5T4 oncofoetal antigen: a target for immunotherapy in cancer

2002 ◽  
Vol 366 (1) ◽  
pp. 353-365 ◽  
Author(s):  
Andrew M. WOODS ◽  
Who W. WANG ◽  
David M. SHAW ◽  
Christopher M. WARD ◽  
Miles W. CARROLL ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Immunohistochemical Analysis ◽  
Surface Expression ◽  
Biological Properties ◽  
Cell Surface Expression ◽  
Mouse Tissues ◽  
Clinical Models ◽  
Restricted Pattern ◽  
5T4 Oncofoetal Antigen

Human 5T4 oncofoetal antigen defined by the murine 5T4 monoclonal antibody is a highly glycosylated protein expressed by trophoblast and a few specialized adult epithelia. Up-regulation of 5T4 expression in some cancers is associated with poor clinical outcome; overexpression of human 5T4 cDNA in epithelial cells can alter their morphology and motility, supporting a role for such functions in cancer and development. A murine model to study 5T4 biology and tumour immunology would be useful. The production of m5T4-specific antibodies, their use in establishing transfected cells and documenting their biological properties in vitro are described. A rat monoclonal antibody specific for mouse 5T4 molecules by ELISA, flow cytometry, immunohistochemistry and immunoprecipitation was isolated and epitope mapped. Similar to its human counterpart, murine 5T4 antigen is a 72kDa glycoprotein (immunoprecipitation and Western blot analysis) and exhibits punctate cell surface expression, dependent upon the integrity of the actin cytoskeleton. Likewise, overexpression of autologous murine 5T4 by B16 F10 melanoma cells and A9 L fibroblasts accentuates the 5T4 phenotype, which is characterized by a spindle-like morphology, increased motility, and reduced adhesion and proliferation rate. Immunohistochemical analysis of adult mouse tissues shows a restricted pattern of expression similar to that of human 5T4 antigen. The murine 5T4 antigen-expressing cell lines and antibody reagents are now being used to explore novel immunotherapies in pre-clinical models and the biology of 5T4 in development.

scholarly journals Mixed glycosidase pretreatment reduces nonspecific binding of antibodies to frozen tissue sections.

1985 ◽  
Vol 33 (7) ◽  
pp. 695-698 ◽  
Author(s):  
L P Andrews ◽  
R K Clark ◽  
I Damjanov
Keyword(s):  
Monoclonal Antibody ◽  
Renal Tissue ◽  
Frozen Sections ◽  
Tissue Sections ◽  
Mouse Tissues ◽  
Background Staining ◽  
Frozen Tissue ◽  
Nonspecific Staining ◽  
Immunohistochemical Studies ◽  
Monoclonal Antibody Binding

Indirect immunohistochemical studies of frozen mouse tissues with mouse monoclonal antibodies yield, in general, suboptimal results primarily because of indiscriminate binding of secondary antibody to all mouse immunoglobulins, i.e., to the monoclonal reagent and to endogenous immunoglobulin nonspecifically trapped in the tissue. To reduce this nonspecific staining, frozen sections of mouse kidney were treated enzymatically. Optimal results were obtained following a 2 hr treatment with 20 mg/ml of mixed glycosidases (MG). This treatment reduced the nonspecific background staining of the interstitial spaces and blood vessels, but did not affect the reactivity of structurally bound immunoglobulin G (IgG) in the glomeruli or alter the reactivity of mouse renal tissue to the monoclonal antibody that recognizes an oligosaccharide antigenic determinant (SSEA-1). Eluates from enzyme-treated frozen tissue sections contained normally immunoreactive IgG in the form of dimers. These data indicate that MG treatment of frozen sections could be safely used to reduce the content of nonstructurally bound immunoglobulins in frozen tissues and thus improve the visualization of specific monoclonal antibody binding.

Partial Inhibition of Platelet Aggregation and Fibrinogen Binding by a Murine Monoclonal Antibody to GPIIIa: Requirement for Antibody Bivalency

1994 ◽  
Vol 72 (06) ◽  
pp. 964-972 ◽  
Author(s):  
Jeffery L Kutok ◽  
Barry S Coller
Keyword(s):  
Monoclonal Antibody ◽  
Platelet Aggregation ◽  
Murine Monoclonal Antibody ◽  
Platelet Glycoprotein ◽  
Igg Antibody ◽  
Surface Receptors ◽  
Partial Inhibition ◽  
Fibrinogen Binding ◽  
Igg Binding ◽  
Agonist Concentration

SummaryWe produced a murine monoclonal antibody, 7H2, and localized its epitope to one or more small regions on platelet glycoprotein (GP) Ilia. 7H2-IgG and 7H2-F(ab’)2 completely inhibit platelet aggregation and fibrinogen binding at low agonist concentrations, but only partially inhibit aggregation and fibrinogen binding at high agonist concentrations; 7H2-Fab has no effect on aggregation or fibrinogen binding at any agonist concentration. 7H2-IgG binds to the entire platelet population as judged by flow cytometry. At near saturating concentrations, ∼40,000 7H2-IgG antibody molecules bind per platelet. In contrast, ∼80,000 7H2 Fab molecules bind per platelet, suggesting that 7H2-IgG binding is bivalent. 7H2 was unable to inhibit fibrinogen binding to purified, immobilized GPIIb/IIIa. These data indicate that the bivalent binding of 7H2 to GPIIIa is required for its partial inhibition of fibrinogen binding to platelets, perhaps through dimerization of GPIIb/IIIa surface receptors (or more complex GPIIb/IIIa redistribution triggered by 7H2 binding) resulting in limited accessibility of fibrinogen to its binding site(s).

High-dose cyclophosphamide inhibition of humoral immune response to murine monoclonal antibody 3F8 in neuroblastoma patients: Broad implications for immunotherapy

2007 ◽  
Vol 48 (4) ◽  
pp. 430-434 ◽  
Author(s):  
Brian H. Kushner ◽  
Irene Y. Cheung ◽  
Kim Kramer ◽  
Shakeel Modak ◽  
Nai-Kong V. Cheung
Keyword(s):  
Monoclonal Antibody ◽  
Immune Response ◽  
Humoral Immune Response ◽  
Murine Monoclonal Antibody ◽  
High Dose ◽  
Humoral Immune

Tumor targeting and pharmacokinetics of unmodified and modified F(ab′)2 fragments of an anti-cea murine monoclonal antibody (IMMU-14)

1994 ◽  
Vol 30 ◽  
pp. 319-320
Author(s):  
Abrar Siddiqui ◽  
Syed M. Quadri ◽  
Gary Griffiths ◽  
David Goldenberg ◽  
Huibert M. Vriesendorp
Keyword(s):  
Monoclonal Antibody ◽  
Tumor Targeting ◽  
Murine Monoclonal Antibody

scholarly journals Clinical evaluation of tumor targeting with the anticarcinoembryonic antigen murine monoclonal antibody fragment, MN-14 F(ab)2

Cancer ◽  
1996 ◽  
Vol 78 (1) ◽  
pp. 157-168 ◽  
Author(s):  
Malik Juweid ◽  
Robert M. Sharkey ◽  
Thomas M. Behr ◽  
Lawrence C. Swayne ◽  
Robert Dunn ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Evaluation ◽  
Tumor Targeting ◽  
Antibody Fragment ◽  
Murine Monoclonal Antibody
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