In vivo antitumor effect of methotrexate conjugated to a monoclonal IgM antibody specific for stage-specific embryonic antigen-1, on MH-15 mouse teratocarcinoma.
Methotrexate (MTX) was coupled to an IgM monoclonal antibody specific for stage-specific embryonic antigen-1 (SSEA-1), and the resulting immunoconjugate (MTX-anti-SSEA-1) was used for in vivo drug targeting in mice bearing MH-15 teratocarcinoma. Immunoconjugates having an average of 65 mol MTX/mol antibody retained full antigen-binding capacity. Mice bearing well-established tumors (approx. 1 g) were treated i.v. using the immunoconjugate. MTX-anti-SSEA-1 at 15 mg/kg of drug had significant antitumor activity with no significant systemic toxicity. Neither an irrelevant isotype-matched conjugate, MTX-MOPC-104E, prepared from the MOPC 104E myeloma protein, nor free MTX injected alone or with either antibody had any significant antitumor effect. These 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.
Persiani
S
S
Department of Surgery, School of Medicine, University of Pittsburgh, PA 15261.
Ballou
B
B
Shen
W C
WC
Ryser
H J
HJ
Reiland
J M
JM
Hakala
T R
TR
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000937:Antigen-Antibody Reactions; D000951:Antigens, Neoplasm / Q000276:immunology; D006017:Glycolipids / Q000276:immunology*; D007075:Immunoglobulin M; D007167:Immunotherapy; D000922:Immunotoxins / Q000627:therapeutic use*; D016256:Lewis X Antigen; D008727:Methotrexate / Q000008:administration & dosage*; D013724:Teratoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D006017:Glycolipids; D007075:Immunoglobulin M; D000922:Immunotoxins; D016256:Lewis X Antigen; D008727:Methotrexate