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In vivo andin vitro antitumor activity of mitomycin C conjugates at 7-N position through a linker containing thiocarbamate bond with CD10 monoclonal antibody

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Biotherapy

Abstract

Through a linker containing thiocarbomate bound to the 7-N position of mitomycin C (MMC), conjugates with a monoclonal antibody to CD10 (NL-1) were prepared, and their antitumor activities were examined. All five conjugates, except one, showedin vitro cytotoxity to two CD10+ lymphoid cell lines superior to MMC. The conjugate displaying the highest cytotoxicity was selected and further tested against three CD10+ and two CD10 lymphoid cell linesin vitro. The conjugate with NL-1 antibody demonstrated higher cytotoxic activity against CD10+ tumor cells than the control conjugate with normal immunoglobulin, while there was no significant difference, when tested against CD10− tumors. The cytotoxic activity of the NL-1 conjugate to CD10+ tumors was significantly blocked by NL-1 antibody.

In vivo antitumor activity of the NL-1 conjugate was then tested against a CD10+ tumor transplanted to nude mice, and side effects were recorded. The NL-1 conjugate (4 mg/kg) showed anin vivo antitumor effect similar to MMC (2 mg/kg), which is at nearly maximal tolerable dose; the latter induced decreases in numbers of leukocytes and platelets, while the former did not, suggesting less side effect by the NL-1 conjugate. Since MMC demonstrates a broad spectrum of antitumor activity, the conjugate, as such, may be applicable for the treatment of cancer patients.

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Abbreviations

ALL:

acute lymphocytic leukemia

CML:

chronic myclocytic leukemia

h:

hour

IgG:

immunoglobulin G

MMC:

mitomycin C

MMC-D:

mitomycin C derivative

PBS:

phosphate buffered saline

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Authors and Affiliations

  1. Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., 411, Shizuoka

    Yasushi Shida, Masami Okabe, Tokuyuki Kuroda & Makoto Morimotol

  2. Aichi Cancer Center Research institute, 464, Nagoya, Japan

    Ryuzo Ueda & Toshitada Takahashi

Authors
  1. Yasushi Shida
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  2. Masami Okabe
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  3. Tokuyuki Kuroda
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  4. Makoto Morimotol
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  5. Ryuzo Ueda
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  6. Toshitada Takahashi
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Shida, Y., Okabe, M., Kuroda, T. et al. In vivo andin vitro antitumor activity of mitomycin C conjugates at 7-N position through a linker containing thiocarbamate bond with CD10 monoclonal antibody. Biotherapy 5, 97–105 (1992). https://doi.org/10.1007/BF02171694

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  • DOI: https://doi.org/10.1007/BF02171694

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