Corpus ID: 13478393

Targeting, internalization, and cytotoxicity of methotrexate-monoclonal anti-stage-specific embryonic antigen-1 antibody conjugates in cultured F-9 teratocarcinoma cells.

@article{Shen1986TargetingIA,
  title={Targeting, internalization, and cytotoxicity of methotrexate-monoclonal anti-stage-specific embryonic antigen-1 antibody conjugates in cultured F-9 teratocarcinoma cells.},
  author={Wei Shen and Byron T. Ballou and Hugues J.-P. Ryser and Thomas R. Hakala},
  journal={Cancer research},
  year={1986},
  volume={46 8},
  pages={
          3912-6
        }
}
Methotrexate (MTX) conjugates of a monoclonal antibody, anti-SSEA-1, containing an average of 45 mol MTX/mol of immunoglobulin M, were prepared by a carbodiimide coupling reaction. Binding experiments indicate that conjugation does not decrease the affinity of the antibody for its antigen. The conjugate strongly inhibits the growth of SSEA-1-bearing F-9 teratocarcinoma cells, with 50% inhibitory dose of 4.5 nM MTX, which makes it more active than free MTX (50% inhibitory dose of 15 nM). The… Expand
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43 Citations

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In vivo antitumor effect of methotrexate conjugated to a monoclonal IgM antibody specific for stage-specific embryonic antigen-1, on MH-15 mouse teratocarcinoma
TLDR
The results indicate that IgMs can be effective drug carriers for tumor targeting in spite of their high molecular mass, and that antigens that are selectively accessible in tumors, even though present in normal tissues, can be suitable targets for in vivo chemoimmunotherapy. Expand
Preparation and in vitro cytotoxicity of a methotrexate‐anti‐MM46 monoclonal antibody conjugate via an oligopeptide spacer
A method was developed by which conjugates of methotrexate (MTX) with antibody were prepared via an oligopeptide spacer which, after internalization of the conjugates into the target cells, would be… Expand
In vitro cytotoxicity of a human serum albumin-mediated conjugate of methotrexate with anti-MM46 monoclonal antibody.
TLDR
The results support the idea that the selective cytotoxicity of aMM46:HSA:MTX is antibody directed and exhibited through lysosomal degradation of the conjugate. Expand
Specific in vitro anti‐tumour activity of methotrexate‐monoclonal antibody conjugates prepared using human serum albumin as an intermediary
TLDR
By increasing the amount of drug bound to antibody, more toxic conjugates were made – an important principle for the use of such conjugate for the treatment of cancer in man. Expand
Tissue localization of methotrexate-monoclonal-IgM immunoconjugates: Anti-SSEA-1 and MOPC 104E in mouse teratocarcinomas and normal tissues
TLDR
Tumor-associated antigens can be suitable targets for antibody-drug conjugates even when present in normal tissues and in large quantities, provided that the antigen innormal tissues are inaccessible. Expand
Nature of linkage and mode of action of methotrexate conjugated with antitumor antibodies: implications for future preparation of conjugates.
TLDR
In combination with hydroxylamine treatment, insertion between MTX and IgG of a linkage capable of ready cleavage in lysosomes deserves exploitation as a method for making potent conjugates with less nonspecific activity. Expand
Selective killing of carcinoembryonic-antigen (CEA)-producing cells in vitro by the immunoconjugate cytorhodin-S and CEA-reactive cytorhodin-S antibody CA208
TLDR
In vitro results indicate that cytorhodin-S may be a good partner in immunoconjugates, however, in vivo animal experiments with the Immunoconjugate revealed that the immunconjugate was not so effective in prolonging survival. Expand
Cytotoxicities of two disulfide-bond-linked conjugates of methotrexate with monoclonal anti-MM46 antibody
TLDR
The cytotoxicity of MTX-Cys-SS-αMM46 was not affected by thiamine pyrophosphate, an inhibitor of the active transport ofMTX across the cell membrane, but was decreased significantly by ammonium chloride, a lysosomotropic amine. Expand
Monensin is obligatory for the cytotoxic action of a disulfide linked methotrexate-anti-transferrin receptor conjugate.
TLDR
Results suggest that the ionophore causes antibody-drug conjugate to bypass the normal transferrin receptor cyclic pathway, allowing sufficient drug to reach, bind to, and inactivate intracellular dihydrofolate reductase. Expand
The use of monoclonal antibody conjugates for the diagnosis and treatment of cancer
TLDR
The prospect of using antibodies as vehicles for isotopes, drugs and toxins only became a reality witb the description of monoclonal antibodies which had some degree of specificity for tumours after xenogenic anti-tumours had little specific reactivity with tumours. Expand
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