A bispecific monoclonal antibody against methotrexate and a human tumour associated antigen augments cytotoxicity of methotrexate-carrier conjugate

A bispecific monoclonal antibody, reactive with methotrexate (MTX) and a tumour associated antigen (gp72) has been produced by fusing spleen cells from MTX immunised mice with 791T/36/3 (anti-gp72) hybridoma. The hybrid antibody was purified from anti-MTX and anti-gp72 antibodies present in the hybr...

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Bibliographic Details
Published in:British journal of cancer 1990-04, Vol.61 (4), p.508-513
Main Authors: Pimm, MV, Robins, RA, Embleton, MJ, Jacobs, E, Markham, AJ, Charleston, A, Baldwin, RW
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal - therapeutic use
Antibody Specificity
Antigens, Neoplasm - immunology
Antineoplastic agents
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cancer Research
Drug Resistance
Epidemiology
experimental-oncology
General aspects
Glycoproteins - immunology
Humans
Medical sciences
Methotrexate - immunology
Methotrexate - therapeutic use
Molecular Medicine
Oncology
Pharmacology. Drug treatments
Serum Albumin - therapeutic use
Tumor Cells, Cultured - drug effects
Tumor Cells, Cultured - immunology
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Description
Summary:A bispecific monoclonal antibody, reactive with methotrexate (MTX) and a tumour associated antigen (gp72) has been produced by fusing spleen cells from MTX immunised mice with 791T/36/3 (anti-gp72) hybridoma. The hybrid antibody was purified from anti-MTX and anti-gp72 antibodies present in the hybridoma culture supernatant by combinations of affinity chromatography on a MTX-agarose immunoabsorbent and stepwise acid elution from Sepharose-Protein A. A particular feature of the present antibody is that it reacts with conjugated MTX; this would allow in vivo targeting of conjugates, increasing many fold the number of molecules of drug carried or localising to pre-targeted antibody. Dual binding between tumour cell surface antigen and MTX was demonstrated by the ability of the hybrid antibody to bridge between tumour cells and MTX as MTX-HSA conjugate, reaction here being detected by flow cytofluorimetry. Purified hybrid antibody specifically enhanced the in vitro cytotoxicity of MTX-HSA for gp72 positive tumour cells.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.1990.115