In Vitro Antibody-Enzyme Conjugates with Specific Bactericidal Activity

Knowles, Daniel M.; Sulivan, T J; Parker, Carol; Williams, Ralph C.

doi:10.1172/jci107318

Cited by 6 publications

(2 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4 Log (12). A polyclonal anti-C. albicans antibody carrying both xanthine oxidase and lactoperoxidase was shown to be cytotoxic (19), and immunoconjugates have been used to target amphotericin B-containing liposomes to C. albicans (7).…”

Section: Methodsmentioning

confidence: 99%

Enzyme immunoconjugates utilizing glucose oxidase and myeloperoxidase are cytotoxic to Candida tropicalis

Casentini-Borocz¹,

Bringman²

1990

Antimicrob Agents Chemother

View full text Add to dashboard Cite

A dual-enzyme immunoconjugate system was evaluated for its cytotoxic effect on Candida tropicalis. Glucose oxidase, which generates hydrogen peroxide in the presence of glucose and oxygen, and myeloperoxidase, which catalyzes the oxidation of halides in the presence of hydrogen peroxide, were each conjugated to a C. tropicalis-specffic monoclonal antibody. Neither the glucose oxidase nor the myeloperoxidase conjugates exhibited any significant cytotoxic effect by themselves. A combination of glucose oxidase conjugate (3.2 ng/ml) and myeloperoxidase conjugate (12.8 ng/ml) in the presence of 5 mg of glucose per ml, 150 mM chloride, and 50 FM iodide was cytotoxic to C. tropicalis, killing 99.9% of the treated sample. Flow cytometry was used to characterize the binding of the conjugates to yeast cells and demonstrated that the binding of both conjugates to the yeast cell surface is required for cytotoxicity. In addition, the concentrations of conjugates required for a cytotoxic effect were below the concentrations required to saturate all of the yeast cell surface antibodybinding sites.

show abstract

Section: Methodsmentioning

confidence: 99%

Enzyme immunoconjugates utilizing glucose oxidase and myeloperoxidase are cytotoxic to Candida tropicalis

Casentini-Borocz¹,

Bringman²

1990

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…In the complete enzyme system, with iodide or other protoxins, glucose oxidase conjugates of rabbit and goat antibodies to HeLa, HEp-2, L, human colonic carcinoma cells (HT-29), and mouse myeloma (MOPC-315) cells have shown toxicity for their homologous cell lines in vitro (1,(7)(8)(9). Antibody-enzyme conjugates have also been shown to have marked cytotoxicity for bacteria (10) and parasites (11). In all of these cell systems immunologically specific cytotoxicity has been obtained and the antibody-enzyme conjugate has been more potent than the unconjugated antibody in the presence of excess complement.…”

mentioning

confidence: 99%

Enzymatic activation and trapping of luminol-substituted peptides and proteins. A possible means of amplifying the cytotoxicity of anti-tumor antibodies.

Parker¹,

Aach²,

Philpott³

1975

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Glutathione and glucose oxidase (EC 1.1.3.4) conjugates containing covalently bound luminol were prepared as prototypes for peptides and proteins with latent, enzyme-activatable chemical reactivity. In the presence of small quantities of activated horseradish peroxidase, conjugated luminol molecules were oxidized to unstable free radicals which reacted rapidly with soluble proteins and cells. These observations are of interest in regard to possible sequential localization reactions in which a few molecules of cell-bound antibody-horseradish peroxidase would be used to catalytically alter and trap many molecules of a second (luminol-substituted) enzyme, toxin, or hapten in the same area, as might be desirable in promoting selective cell destruction.Recent studies have indicated that it is feasible to attach toxins to antitumor antibodies as a means of amplifying selective cytotoxicity (1-4), an idea first proposed by Paul Ehrlich in 1906 (5). We have suggested that it may be preferable to attacfi the antibody to an exogenous enzyme capable of converting a protoxin to a toxin, rather than directly to a toxin (1,6,7). This would permit the activity of the antibody to be catalytically amplified, providing for effective toxicity in situations in which only a limited number of conjugated antibody molecules can be localized on the cell surface. Particularly interesting results have been obtained with conjugates of antibody to glucose oxidase, a hydrogen peroxide generating enzyme with a very high turnover number. When glucose oxidase is attached through specific antibody to a target cell, and appropriate cofactors (glucose, 02, lactoperoxidase, and inorganic iodide) are added, the cell is iodinated and cell death occurs. In the complete enzyme system, with iodide or other protoxins, glucose oxidase conjugates of rabbit and goat antibodies to HeLa, HEp-2, L, human colonic carcinoma cells , and mouse myeloma (MOPC-315) cells have shown toxicity for their homologous cell lines in vitro (1, 7-9). Antibody-enzyme conjugates have also been shown to have marked cytotoxicity for bacteria (10) and parasites (11). In all of these cell systems immunologically specific cytotoxicity has been obtained and the antibody-enzyme conjugate has been more potent than the unconjugated antibody in the presence of excess complement.In order to exploit the full potential of enzyme-mediated cytotoxicity in vivo, it will be necessary to localize as many enzyme molecules as possible in the tumor. One approach would be the utilization of a sequential localization reaction in which a few molecules of antibody-enzyme conjugate, specifically bound in the tumor, would be used to catalytically alter and trap many more molecules of a second enzyme in the same area. This might be accomplished by attaching a chemically unreactive organic substituent on the surface of the second enzyme and converting it to a highly reactive molecule at the level of the tumor surface. A theoretical scheme is shown in Fig. 1; El-Ab is antibody-first enzyme conjugate;...

show abstract

Antibodies as Antibacterial Molecules: The New Era of Antibody-Mediated Immunity

Tasin

Haque

Mandal

2022

Alternatives to Antibiotics

View full text Add to dashboard Cite

In Vitro Antibody-Enzyme Conjugates with Specific Bactericidal Activity

Cited by 6 publications

References 27 publications

Enzyme immunoconjugates utilizing glucose oxidase and myeloperoxidase are cytotoxic to Candida tropicalis

Enzyme immunoconjugates utilizing glucose oxidase and myeloperoxidase are cytotoxic to Candida tropicalis

Enzymatic activation and trapping of luminol-substituted peptides and proteins. A possible means of amplifying the cytotoxicity of anti-tumor antibodies.

Antibodies as Antibacterial Molecules: The New Era of Antibody-Mediated Immunity

Contact Info

Product

Resources

About