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Targeting cancer chemotherapy using a monoclonal antibody (NCC‐LU‐243) conjugated with mitomycin C
Author(s) -
Kubota Tetsuro,
Yamamoto Takaaki,
Takahara Tetsuya,
Furukawa Toshiharu,
Ishibiki Kyuya,
Kitajima Masaki,
Shida Yasui,
Nakatsubo Hiroshi
Publication year - 1992
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.2930510203
Subject(s) - immunoconjugate , monoclonal antibody , antigen , mitomycin c , in vivo , microbiology and biotechnology , medicine , antibody , in vitro , immunotoxin , cancer research , immunology , biology , biochemistry , surgery
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>‐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. © 1992 Wiley‐Liss, Inc.