Open AccessTumor Localization and in vivo Antitumor Activity of the Immunoconjugate Composed of Anti‐human Colon Cancer Monoclonal Antibody and Mitomycin C‐Dextran Conjugate
Author(s) -
Noguchi Akinori,
Takahashi Toshio,
Yamaguchi Toshiharu,
Kitamura Kazuya,
Takakura Yoshinobu,
Hashida Mitsuru,
Sezaki Hitoshi
Publication year - 1991
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1991.tb01832.x
Subject(s) - immunoconjugate , in vivo , conjugate , dextran , monoclonal antibody , spleen , mitomycin c , mononuclear phagocyte system , pharmacokinetics , chemistry , distribution (mathematics) , microbiology and biotechnology , in vitro , antibody , pharmacology , pathology , medicine , biology , immunology , biochemistry , mathematical analysis , mathematics , surgery
The tissue distribution and in vivo antitumor activity of a novel monoclonal antibody‐mitomycin C conjugate (A7‐MMCD) composed of anti‐human MAb A7 and MMC‐dextran conjugate were investigated using tumor‐bearing mice. A7‐MMCD was prepared via an anionic dextran intermediate for the purpose of keeping the non‐specific uptake by the reticuloendothelial system to a minimum, 111 n‐labeled A7‐MMCD showed about a 5‐times‐greater accumulation in SW1116 (targeted tumor) than in S180 (non‐targeted tumor) 48 h after injection, and produced a tumor‐to‐blood ratio which was 3 times higher in SW1116‐bearing mice than in S180‐bearing mice 96 h after injection. Accumulations in the liver, spleen, and kidney were also observed to some extent. Pharmacokinetic analysis revealed that A7‐MMCD had nearly the same properties in the body as MMCD an (MMCD with an anionic charge), i.e. those of a negatively charged macromolecule. Both A7‐MMCD and MMCD an had relatively similar tissue uptake rate indices for the liver and spleen. The tumor uptake rate index for SW1116 was about 2.5 times greater than that for S180, and the total amount of 111 In‐A7‐MMCD accumulated in SW1116 was calculated to be approximately 5 times greater than the amount in S180. These results indicated that A7‐MMCD could achieve site‐specific targeting in the body. Furthermore, in the therapeutic experiment using SW1116 implanted subcutaneously, A7‐MMCD suppressed tumor growth significantly, compared to free MMC and MMCD an . These results suggest that in designing an monoclonal antibody‐drug conjugate via an intermediary, the physicochemical properties of intermediate macromolecules must also be taken into consideration to obtain a high degree of efficacy in vivo.