PURPOSE: Immunoenzymosomes are tumor-targeted immunoliposomes bearing enzymes on their surface. These enzymes are capable of converting relatively nontoxic prodrugs into active cytostatic agents. The aims of this study were to compare the enzyme delivery capability of immunoenzymosomes with that of the corresponding antibody-enzyme conjugate and to evaluate whether immunoenzymosomes are able to mount a strong bystander effect. METHODS: Immunoenzymosomes exposing Fab' fragments of the monoclonal antibody 323/A3 and the bacterial enzyme beta-glucuronidase or the corresponding antibody-enzyme conjugate were incubated with OVCAR-3 cells (human ovarian carcinoma cells). Cell-associated enzymatic activity and the in vitro antiproliferative effect of a glucuronide prodrug of doxorubicin (DOX-GA3) were determined. RESULTS: At equal numbers of carrier units, the cell-associated enzymatic activity achieved by using immunoenzymosomes was 15-fold higher than that obtained after incubation with the corresponding antibody-enzyme conjugate. Increasing the amount of antibody-enzyme conjugate added to the cells could not compensate for their lower enzyme delivery capability. Immunoenzymosomes were able to induce inhibition of cell growth not only of tumor cells to which immunoenzymosomes were bound but also of a large number of neighboring cells. CONCLUSIONS: Immunoenzymosomes are able (a) to target prodrug-converting enzymes more efficiently to tumor cells than the corresponding antibody-enzyme conjugate and (b) to mount a strong bystander effect.
PURPOSE: Immunoenzymosomes are tumor-targeted immunoliposomes bearing enzymes on their surface. These enzymes are capable of converting relatively nontoxic prodrugs into active cytostatic agents. The aims of this study were to compare the enzyme delivery capability of immunoenzymosomes with that of the corresponding antibody-enzyme conjugate and to evaluate whether immunoenzymosomes are able to mount a strong bystander effect. METHODS: Immunoenzymosomes exposing Fab' fragments of the monoclonal antibody 323/A3 and the bacterial enzyme beta-glucuronidase or the corresponding antibody-enzyme conjugate were incubated with OVCAR-3 cells (humanovarian carcinoma cells). Cell-associated enzymatic activity and the in vitro antiproliferative effect of a glucuronide prodrug of doxorubicin (DOX-GA3) were determined. RESULTS: At equal numbers of carrier units, the cell-associated enzymatic activity achieved by using immunoenzymosomes was 15-fold higher than that obtained after incubation with the corresponding antibody-enzyme conjugate. Increasing the amount of antibody-enzyme conjugate added to the cells could not compensate for their lower enzyme delivery capability. Immunoenzymosomes were able to induce inhibition of cell growth not only of tumor cells to which immunoenzymosomes were bound but also of a large number of neighboring cells. CONCLUSIONS: Immunoenzymosomes are able (a) to target prodrug-converting enzymes more efficiently to tumor cells than the corresponding antibody-enzyme conjugate and (b) to mount a strong bystander effect.
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