Effects of idiotypic human anti-mouse antibody against in vitro binding and antitumor activity of a monoclonal antibody-drug conjugate.
OBJECTIVE
Because the HAMA (human anti-mouse antibody) response following administration of murine monoclonal antibodies represents mainly isotypic HAMA production, idiotypic HAMA responses have not been thoroughly analyzed.


METHODS
In the present study we examined the effect of idiotypic HAMA that arose in patients who had repeatedly received murine monoclonal antibody conjugated to an anticancer drug against in vitro binding and antitumor activity of the conjugate. HAMA that had developed after administration of tumor-specific murine monoclonal antibody A7 conjugated with neocarzinostatin were measured in patient serum. The inhibitory effect of HAMA on tumor binding and antitumor activity of the A7-neocarzinostatin conjugate was examined in cultures of human colonic carcinoma cells.


RESULTS
The serum concentration of idiotypic HAMA in patients administered A7-neocarzinostatin was significantly higher than that in a control group. Binding activity and antitumor activity of A7-neocarzinostatin against target cells was reduced in the presence of sera containing HAMA.


CONCLUSIONS
Repeated use of A7-neocarzinostatin can be expected to show less antitumor effect than the first use of the conjugate.
Otsuji
Eigo
E
Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachi, Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan. otsuji@koto.kpu-m.ac.jp
Tsuruta
Hiroshi
H
Toma
Atsushi
A
Kobayashi
Shinichiro
S
Okamoto
Kazuma
K
Yata
Yoshihiro
Y
Yamagishi
Hisakazu
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D001666:Binding Sites, Antibody; D003110:Colonic Neoplasms / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics*; D051379:Mice; D014407:Tumor Cells, Cultured; D009353:Zinostatin / Q000493:pharmacokinetics*
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D009353:Zinostatin