Cytotoxicities of two disulfide-bond-linked conjugates of methotrexate with monoclonal anti-MM46 antibody

  title={Cytotoxicities of two disulfide-bond-linked conjugates of methotrexate with monoclonal anti-MM46 antibody},
  author={Naoji Umemoto and Yoshinori Kato and Takeshi Hara},
  journal={Cancer Immunology, Immunotherapy},
SummaryIn studies on (antitumor antibody)-drug conjugates as potential antitumor agents, the amide derivatives of methotrexate (MTX) with cysteine and with 2-mercaptoethylamine (cysteamine) (MTX-Cys and MTX-MEA, respectively) were linked via a disulfide bond with a monoclonal antibody (αMM46) to a mouse mammary tumor MM46 with attached 3-(2-pyridyldithio) propionyl groups to give conjugates of MTX with αMM46 (MTX-Cys-SS-αMM46 and MTX-MEA-SS-αMM46, respectively). These two conjugates are both… 
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
Synthesis and biological evaluation of disulfide-linked HPMA copolymer-mesochlorin e6 conjugates.
The synthesized conjugates demonstrated a time-dependent reductive cleavage with an accompanying increase in the quantum yield of singlet oxygen generation on exposure to DTT and hold promise as clinically relevant drug delivery systems for photodynamic therapy of cancer.
Drug targeting by macromolecules without recognition unit?
Two examples of methotrexate and daunomycin conjugates will be discussed to show the effect of the chemical structure of branched chain polypeptides on the uptake and antitumour or antiparasitic (Leishmania donovani infection) efficacy of conjugate.
Tissue localization of methotrexate-monoclonal-IgM immunoconjugates: Anti-SSEA-1 and MOPC 104E in mouse teratocarcinomas and normal tissues
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.


In vitro cytotoxicity of a human serum albumin-mediated conjugate of methotrexate with anti-MM46 monoclonal antibody.
The results support the idea that the selective cytotoxicity of aMM46:HSA:MTX is antibody directed and exhibited through lysosomal degradation of the conjugate.
Monensin is obligatory for the cytotoxic action of a disulfide linked methotrexate-anti-transferrin receptor conjugate.
Production of a monoclonal antibody-methotrexate conjugate utilizing dextran T-40 and its biologic activity.
The results indicate that the MTX-(H-l) conjugate binds to the cell surface antigen by its antibody action and exerts greater MTX cytotoxicity than free MTX in vitro.
Studies of methotrexate-monoclonal antibody conjugates for immunotherapy.
MTX-antibody complexes can be successfully produced and can be used for the immunotherapy of tumors and impaired the growth of established tumors in vivo.
Target-selective cytotoxicity of methotrexate conjugated with monoclonal anti-MM46 antibody
SummaryIn studies on antitumor antibody-cytotoxic drug conjugates as potential tumor-selective cytotoxic agents, methotrexate (MTX) was conjugated via its active ester derivative with a murine
Covalent binding of methotrexate to immunoglobulins and the effect of antibody-linked drug on tumor growth in vivo.
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.
Targeting, internalization, and cytotoxicity of methotrexate-monoclonal anti-stage-specific embryonic antigen-1 antibody conjugates in cultured F-9 teratocarcinoma cells.
Results indicate that the MTX antibody conjugate binds specifically to F-9 cells, and is internalized and intracellularly degraded to release a small molecular active drug.
Importance of the antigen-binding valency and the nature of the cross-linking bond in ricin A-chain conjugates with antibody.
Results suggest that divalency in antigen-binding and susceptibility of the cross-linking bond to cleavage by mercapto reagent are desirable for high potency.
Effect of methotrexate-monoclonal anti-prostatic acid phosphatase antibody conjugate on human prostate tumor.
It is suggested that MTX conjugated to monoclonal anti-PAP antibody could be a potential reagent for experimental immunochemotherapy of prostate tumor, should the initial in vivo data be extended and confirmed.
Preparation and properties of a drug‐carrier‐antibody conjugate showing selective antibody‐directed cytotoxicity in vitro
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.