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…
44 Citations
In vivo antitumor effect of methotrexate conjugated to a monoclonal IgM antibody specific for stage-specific embryonic antigen-1, on MH-15 mouse teratocarcinoma
- BiologyCancer Immunology, Immunotherapy
- 2004
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.
Preparation and in vitro cytotoxicity of a methotrexate‐anti‐MM46 monoclonal antibody conjugate via an oligopeptide spacer
- Biology, ChemistryInternational journal of cancer
- 1989
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…
In vitro cytotoxicity of a human serum albumin-mediated conjugate of methotrexate with anti-MM46 monoclonal antibody.
- Biology, ChemistryCancer research
- 1987
The results support the idea that the selective cytotoxicity of aMM46:HSA:MTX is antibody directed and exhibited through lysosomal degradation of the conjugate.
Selective killing of carcinoembryonic-antigen (CEA)-producing cells in vitro by the immunoconjugate cytorhodin-S and CEA-reactive cytorhodin-S antibody CA208
- Biology, ChemistryCancer Immunology, Immunotherapy
- 2005
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.
Cytotoxicities of two disulfide-bond-linked conjugates of methotrexate with monoclonal anti-MM46 antibody
- Biology, ChemistryCancer Immunology, Immunotherapy
- 2004
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.
Monensin is obligatory for the cytotoxic action of a disulfide linked methotrexate-anti-transferrin receptor conjugate.
- Biology, ChemistryBiochemical and biophysical research communications
- 1988
The use of monoclonal antibody conjugates for the diagnosis and treatment of cancer
- BiologyImmunology and cell biology
- 1987
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.
Sensitivity of newly established colorectal cell lines to cytotoxic drugs and monoclonal antibody drug conjugates.
- Biology, MedicineBritish Journal of Cancer
- 1987
This is the first report to show that newly established cell lines that are resistant to classical chemotherapeutic agents are rendered sensitive when the drug enters the cell as a drug monoclonal antibody carrier.
Monoclonal antibody drug immunoconjugates for targeted treatment of cancer
- Biology, ChemistryCancer Immunology, Immunotherapy
- 2003
This review concentrates on the properties of the tumor and the characteristics of the mAb, linker, and drugs that influence the efficacy, potency, and selectivity of immunconjugates selected for cancer treatment.
Review : Molecular Design of Methotrexate-Antibody Conjugates for Targeted Cancer Treatment
- Chemistry, Biology
- 1992
This article focuses on the molecular design of methotrexate (MTX) conjugates, their rationale, and methods of synthesis, and recommended as a drug suitable for conjugation based on several considerations.
References
SHOWING 1-10 OF 35 REFERENCES
Covalent binding of methotrexate to immunoglobulins and the effect of antibody-linked drug on tumor growth in vivo.
- Biology, ChemistryCancer research
- 1981
The demonstrated superiority of the active ester method in producing active conjugates prompted us to use this technique for linking MTX to a rabbit IgG antibody against the mouse EL4 lymphoma.
Conjugation of methotrexate to poly(L-lysine) increases drug transport and overcomes drug resistance in cultured cells.
- Biology, ChemistryProceedings of the National Academy of Sciences of the United States of America
- 1978
It is shown that in methotrexate-resistant cells the intracellular release of active drug after uptake of conjugate is of the same order of magnitude as the uptake of free drug by transport-proficient cells and, hence, that the drug resistance due to deficient transport can be totally overcome.
Uptake of methotrexate linked to polyclonal and monoclonal antimelanoma antibodies by a human melanoma cell line.
- Biology, MedicineJournal of the National Cancer Institute
- 1985
Binding sites for MoAb 225.28S were more efficient for internalization of MTX than were those for the two polyclonal antibody preparations, and the order of uptake by the three antibody conjugates corresponded to the amount of conjugate bound at equilibrium at 0 degrees C and to the immunofluorescence titers.
Antibodies as Carriers of Cancer Chemotherapeutic Agents a
- Biology, ChemistryAnnals of the New York Academy of Sciences
- 1985
Evidence is provided that anti-TAA antibodies or their reactive fragments can selectively deliver cytotoxic amounts of drugs or protein toxins to target tumor cells in vitro and, at least in some instances, also in U ~ U O .
Preparation and properties of a drug‐carrier‐antibody conjugate showing selective antibody‐directed cytotoxicity in vitro
- Biology, ChemistryInternational journal of cancer
- 1983
Results indicate that a drug‐carrier antibody conjugate can be synthesized which has all the in vitro properties theoretically necessary for a successful antibody‐targeted cytotoxic agent.
Poly (L-lysine) and poly (D-lysine) conjugates of methotrexate: different inhibitory effect on drug resistant cells.
- Biology, ChemistryMolecular pharmacology
- 1979
Conjugation of methotrexate to poly(L-lysine) markedly increases its cellular uptake and offers a new way to overcome drug resistance related to deficient transport and to give rise in the cell to a pharmacologically active breakdown product.
Tumour cell-antibody interactions. II. In vitro studies.
- Biology, MedicineImmunology
- 1982
The interaction of L5178Y thymic lymphoma cells syngeneic to DBA/2 mice and of normal thymocytes with goat IgG antibodies was studied in vitro. Viable tumour and normal cells exerted a rapid,…
Selective protection against the cytotoxicity of methotrexate and methotrexate-poly(lysine) by thiamine pyrophosphate, heparin and leucovorin.
- Biology, ChemistryLife sciences
- 1981
Membrane transport of methotrexate in human lymphoblastoid cells.
- MedicineCancer research
- 1978
The elucidation of a second route of MTX transport at high dose concentrations in human neoplastic cells may explain the apparent efficacy of high-dose MTX in MTX-“resistant” tumors.
Localization of I-131-labeled tumor-specific monoclonal antibody in the tumor-bearing BALB/c mouse.
- BiologyJournal of nuclear medicine : official publication, Society of Nuclear Medicine
- 1980
The localization of an iodine-131-labeled, hybridoma-derived monoclonal antibody in the MH-15 teratocarcinoma-bearing BALB/c mouse is reported and the relationship between the optimal imaging time and localization kinetics is discussed.