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 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.
Pimm
M V
MV
Cancer Research Campaign Laboratories, University of Nottingham, UK.
Robins
R A
RA
Embleton
M J
MJ
Jacobs
E
E
Markham
A J
AJ
Charleston
A
A
Baldwin
R W
RW
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D008727:Methotrexate / Q000276:immunology / Q000627:therapeutic use*; D012709:Serum Albumin / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006023:Glycoproteins; D012709:Serum Albumin; C040811:methotrexate-serum albumin; C047052:tumor-associated antigen 72; D008727:Methotrexate