Open AccessIn vivo Efficacy of Neocarzinostatin Coupled with Fab Human/Mouse Chimeric Monoclonal Antibody A7 against Human Colorectal Cancer
Author(s) -
Yamaguchi Toshiharu,
Tsurumi Hiroshi,
Kotani Tatsuya,
Yamaoka Nobuki,
Otsuji Eigo,
Kitamura Kazuya,
Takahashi Toshio
Publication year - 1994
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.1349-7006.1994.tb02078.x
Subject(s) - neocarzinostatin , monoclonal antibody , immunoconjugate , conjugate , in vivo , toxicity , antibody , chemistry , antigen , monoclonal , pharmacology , colorectal cancer , chemotherapy , cancer research , microbiology and biotechnology , cancer , immunology , medicine , biology , biochemistry , mathematical analysis , dna , mathematics , organic chemistry
The anticancer polypeptide neocarzinostatin (NCS) was covalently coupled to a human/mouse chimeric Fab A7 monoclonal antibody (chFabA7) and the in vivo efficacy of this conjugate was examined. NCS concentration assay was carried out, and acute toxicity and tumoricidal effects were examined. The concentration assay, using anti‐NCS monoclonal antibody, revealed that administration of the chA7Fab conjugate leads to a greater blood retention and a higher tumor accumulation of NCS, when compared to free NCS administration. The tumoricidal effect of chA7Fab‐NCS was higher than that of either free NCS or the saline control, against antigen‐positive tumors. In antigen‐negative tumors there was no difference in toxic effect among the three preparations. Values of LD 50 , reflecting acute toxicity, were 5050 U/kg and 3600 U/kg for the chA7Fab‐NCS and the free NCS, respectively. These results suggest that chFahA7‐NCS may be a promising tool for targeting cancer chemotherapy.