Targeting cancer chemotherapy using a monoclonal antibody (NCC-LU-243) conjugated with mitomycin C.
Two kinds of immunoconjugate (T-3M and T-11M) of murine monoclonal antibody with mitomycin C (MMC) were developed using spacers containing a disulfide (T-3M) or thiocarbamate (T-11M) bond. A murine monoclonal antibody (NCC-LU-243) raised against a human small cell lung carcinoma cell line, Lu-24, in nude mice, is an IgG2a monoclonal antibody that recognizes a 145-kDa protein on the cell surface membrane. T-3M and T-11M showed affinity for the LU-243 antigen-positive H-69 cell line but not for the antigen-negative Lu-65 cell line in vitro. In the in vitro MTT assay, the order of efficacy of these compounds was T-11M > T-3M > MMC against antigen positive H-69 and T-11M = MMC > T-3M against antigen-negative K562. When antigen-positive H-69 was transplanted into nude mice for in vivo assay, the maximum tolerated dose of T-3M was twice as high than that of the parent compound MMC. Furthermore, T-3M showed higher antitumor activity against antigen-positive H-69 than MMC conjugated with a non-specific rabbit IgG in vivo. When the maximum tolerated doses of T-3M and MMC were administered to H-69-bearing nude mice, the effect of T-3M was superior to that of MMC, whereas no differences were observed between the antitumor activity of T-3M and MMC against antigen- negative MX-1, a human breast carcinoma. These two immunoconjugates of monoclonal antibody with mitomycin C are thought to be useful for targeting cancer chemotherapy against human small cell lung carcinomas.
Kubota
T
T
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Yamamoto
T
T
Takahara
T
T
Furukawa
T
T
Ishibiki
K
K
Kitajima
M
M
Shida
Y
Y
Nakatsubo
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000922:Immunotoxins / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D016685:Mitomycin / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D000922:Immunotoxins; D016685:Mitomycin