Antigenicity and drug susceptibility of human osteogenic sarcoma cells “escaping” a cytotoxic methotrexate-albumin-monoclonal antibody conjugate

Embleton, M. J.; Garnett, Martin C.; Jacobs, Elizabeth R.; Baldwin, Robert

doi:10.1038/bjc.1984.89

Cited by 6 publications

(4 citation statements)

References 11 publications

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“…As shown in Figure 1, the MTX-HSA conjugate was almost 2 orders of magnitude less toxic than free MTX, consistent with previous reports (Garnett et al, 1983). The a r m antibody- linked conjugate was only marginally more toxic than MTX-HSA and much less so than free MTX, in marked contrast to previous studies with MTX-HSA-791T/36 conjugates which showed levels of cytotoxicity for 791T cells approaching, or higher than, that of the free drug (Garnett et al, 1983;Garnett and Baldwin, 1 9 8 6~;Embleton et al, 1984).…”

Section: Cytotoxicity Tests With Methotrexate Conjugatescontrasting

confidence: 60%

“…In one experiment a clonogenic assay was employed (Embleton et al, 1984) in which 200 target cells were seeded in 30-mm dishes, followed 4 hr later by addition of drug or conjugate and further incubation for 6 days. Cell colonies were fixed with methanol, stained with 0.1 % aqueous crystal violet and counted under x SO stereoscopic magnification.…”

Section: Cytotoxicity Testsmentioning

confidence: 99%

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Unsuitability of monoclonal antibodies to oncogene proteins for anti‐tumour drug‐targeting

Embleton¹,

Habib²,

Garnett³

et al. 1986

Intl Journal of Cancer

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Monoclonal antibodies (MAbs) to ras, sis, erb-B, src, myb and myc oncoproteins were evaluated for their potential to target anti-cancer drugs to malignant cells. Each antibody was tested for reactivity against both fixed and viable cultured human tumour cells by immunofluorescence, and all reacted against a variety of fixed tumour cell preparations. Reactions were also observed against fixed non-malignant cells. None, however, reacted significantly with viable cells. Two antibodies (against ras and myc proteins) were tested for their ability to localize to tumour xenografts in nude mice, and conjugates were constructed by linking these antibodies to methotrexate using human serum albumin as an intermediate carrier. Neither antibody localized to tumour in vivo, and the methotrexate conjugates were not significantly cytotoxic for tumour cells in vitro, in contrast to similar conjugates simultaneously prepared with a proven anti-tumour MAb (791T/36). It was concluded that currently available MAbs to oncogene proteins are not suitable vectors for targeting cytotoxic agents to tumour cells.

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Section: Cytotoxicity Tests With Methotrexate Conjugatescontrasting

confidence: 60%

Section: Cytotoxicity Testsmentioning

confidence: 99%

Unsuitability of monoclonal antibodies to oncogene proteins for anti‐tumour drug‐targeting

Embleton¹,

Habib²,

Garnett³

et al. 1986

Intl Journal of Cancer

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“…This assay has been shown to give results qualitatively equivalent to those obtained using clonogenic assays with MTX and MTX-conjugates (Garnett et al, 1983;Embleton et al, 1984;Embleton & Garnett, 1985). (Roe et al, 1985).…”

Section: Chemicalsmentioning

confidence: 73%

Monoclonal antibody targeting of methotrexate (MTX) against MTX-resistant tumour cell lines

Affleck

Embleton²

1992

Br J Cancer

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“…By flow cytometry, we showed that mAb3A33 antibody substituted with several MDP-polymer molecules were able to bind target cells as well as native mAb3A33 antibody and that the substitution of the monoclonal antibody with MDP-polymer molecules did not significantly impair the binding capacity of the antibody. Indirect conjugation of drugs to monoclonal antibodies via intermediate carriers have been reported to increase the amount of drug attached to antibody without impairing its antigen-binding activity: human serum albumin (27)(28)(29)(30)(31)(32)(33), dextran (34)(35)(36)(37)(38)(39), poly(L-glutamate acid) (40), a copolymer of N-(2-hydroxypropyl)methacrylamide containing an oligopeptide sequence (41), and succinylated polylysine (42) were used as intermediate carriers. In this paper, we used gluconoylated poly(L-lysine), a nonimmunogenic (43) and neutral polymer; the gluconoylation prevents a nonspecific binding to cells and increases the water solubility of poly(L-lysine) (11).…”

Section: Discussionmentioning

confidence: 99%

Activation of mouse macrophages by muramyl dipeptide coupled with an anti-macrophage monoclonal antibody

Midoux

Martin²,

Collet³

et al. 1992

Bioconjugate Chem.

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A rat IgG2a monoclonal antibody (mAb3A33) directed against the mouse Mac-1 antigen was conjugated with muramyl dipeptide (MDP) by using an intermediate polymer; under such conditions 75 MDP molecules were bound to one antibody molecule. A poly(L-lysine) polymer substituted with muramyl dipeptide and 3-(2-pyridyldithio)propionyl residues were prepared, the remaining lysine epsilon-amino groups were acylated with D-gluconolactone, leading to a neutral polymer; then a few polymer conjugates were coupled to mAb3A33 via a disulfide bridge. The binding capacity of the monoclonal antibody was preserved after conjugation with MDP-polymer molecules. Mouse peritoneal macrophages, incubated for 24 h with MDP-mAb3A33 conjugate became cytostatic against P815 mastocytoma cells, whereas unconjugated mAb3A33 and MDP-bound to a nonspecific rat IgG2a were ineffective. An enhancement of the cytostatic activity induced by MDP-mAb3A33 conjugate was obtained in the presence of gamma-IFN. These results show that several tens of MDP molecules can be linked to a macrophage-specific monoclonal antibody by using a neutral intermediate polymer without impairing the binding antibody capacity and that this type of MDP conjugate can efficiently activate macrophages and therefore could be the basis of the development of new antitumor therapy.

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Antigenicity and drug susceptibility of human osteogenic sarcoma cells “escaping” a cytotoxic methotrexate-albumin-monoclonal antibody conjugate

Cited by 6 publications

References 11 publications

Unsuitability of monoclonal antibodies to oncogene proteins for anti‐tumour drug‐targeting

Unsuitability of monoclonal antibodies to oncogene proteins for anti‐tumour drug‐targeting

Monoclonal antibody targeting of methotrexate (MTX) against MTX-resistant tumour cell lines

Activation of mouse macrophages by muramyl dipeptide coupled with an anti-macrophage monoclonal antibody

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