Targeting cancer chemotherapy using a monoclonal antibody (NCC-LU-243) conjugated with mitomycin C

T. Kubota, T. Yamamoto, I. Takahara, Toshiharu Furukawa, K. Ishibiki, M. Kitajima, Y. Shida, H. Nakatsubo

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)75-80
Number of pages6
JournalJournal of Surgical Oncology
Volume51
Issue number2
DOIs
Publication statusPublished - 1992

Fingerprint

Mitomycin
Monoclonal Antibodies
Drug Therapy
Neoplasms
Nude Mice
Immunoconjugates
Maximum Tolerated Dose
Small Cell Lung Carcinoma
Antigens
Cell Line
Thiocarbamates
Disulfides
Immunoglobulin G
Cell Membrane
Breast Neoplasms
Rabbits
H antigen

Keywords

  • mitomycin C
  • nude mouse
  • small cell lung carcinoma

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Targeting cancer chemotherapy using a monoclonal antibody (NCC-LU-243) conjugated with mitomycin C. / Kubota, T.; Yamamoto, T.; Takahara, I.; Furukawa, Toshiharu; Ishibiki, K.; Kitajima, M.; Shida, Y.; Nakatsubo, H.

In: Journal of Surgical Oncology, Vol. 51, No. 2, 1992, p. 75-80.

Research output: Contribution to journalArticle

Kubota, T, Yamamoto, T, Takahara, I, Furukawa, T, Ishibiki, K, Kitajima, M, Shida, Y & Nakatsubo, H 1992, 'Targeting cancer chemotherapy using a monoclonal antibody (NCC-LU-243) conjugated with mitomycin C', Journal of Surgical Oncology, vol. 51, no. 2, pp. 75-80. https://doi.org/10.1002/jso.2930510203
Kubota, T. ; Yamamoto, T. ; Takahara, I. ; Furukawa, Toshiharu ; Ishibiki, K. ; Kitajima, M. ; Shida, Y. ; Nakatsubo, H. / Targeting cancer chemotherapy using a monoclonal antibody (NCC-LU-243) conjugated with mitomycin C. In: Journal of Surgical Oncology. 1992 ; Vol. 51, No. 2. pp. 75-80.
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AU - Shida, Y.

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AB - 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.

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