Decreased production of anti-mouse antibody after administration of human/mouse chimeric monoclonal antibody-neocarzinostatin conjugate to human.
OBJECTIVE
One problem that has been encountered with the use of murine Mabs is the development of a human anti-mouse antibody (HAMA) which lead to serious problems such as anaphylaxis. In order to evaluate the decreased HAMA production after administration of Fab fragments of chimeric monoclonal antibody, Fab fragments of chimeric Mab A7 (chA7Fab) was administered as neocarzinostatin (NCS) conjugate to seven patients with colonic cancer.


METHODS
The in vivo pharmacokinetics of chA7Fab and HAMA production was examined. These patients received an infusion of 4,000 U: dose of NCS (18 mg: dose of chA7Fab).


RESULTS
The plasma disappearance curves showed that chA7Fab-NCS was more rapidly cleared than A7-NCS. The chA7Fab-NCS did not elicit of HAMA in two of seven evaluable patients. The chA7Fab-NCS NCS elicited low levels of HAMA in five of seven evaluable patients. In contrast, A7-NCS elicited high levels of HAMA in all patients tested. Anti-isotype HAMA was not seen in seven evaluable patients tested with chA7Fab-NCS, while A7-NCS elicited high levels in all patients tested.


CONCLUSIONS
This study demonstrates the reduced immunogenicity and shorter clearance time of chA7Fab-NCS compared to A7-NCS.
Yata
Yoshihiro
Y
Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji Kamigyo-ku, Kyoto, Japan.
Otsuji
Eigo
E
Okamoto
Kazuma
K
Tsuruta
Hiroshi
H
Kobayashi
Shinichiro
S
Toma
Atsushi
A
Yamagishi
Hisahazu
H
D000230:Adenocarcinoma / Q000276:immunology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics*; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis* / Q000187:drug effects; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D015179:Colorectal Neoplasms / Q000276:immunology*; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics*; D007140:Immunoglobulin Fab Fragments; D008297:Male; D051379:Mice; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics*; D009353:Zinostatin / Q000493:pharmacokinetics*
D000903:Antibiotics, Antineoplastic; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D011993:Recombinant Fusion Proteins; D009353:Zinostatin