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Titolo:
Enhancement of tumor uptakes by stabilized Fab homo-oligomers of a chimeric monoclonal antibody against carcinoembryonic antigen
Autore:
Kamigaki, T; Ajiki, T; Yamamoto, M; Kuroda, Y;
Indirizzi:
Kobe Univ, Sch Med, Dept Surg 1, Chuo Ku, Kobe, Hyogo 6500017, Japan Kobe Univ Kobe Hyogo Japan 6500017 1, Chuo Ku, Kobe, Hyogo 6500017, Japan
Titolo Testata:
INTERNATIONAL JOURNAL OF ONCOLOGY
fascicolo: 1, volume: 14, anno: 1999,
pagine: 139 - 144
SICI:
1019-6439(199901)14:1<139:EOTUBS>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
PANCREATIC-CARCINOMA; IMMUNE-RESPONSE; NUDE-MICE; CEA; LOCALIZATION; FRAGMENTS; PROTEIN; THERAPY; LINKAGES; KINETICS;
Keywords:
Fab oligomer; chimeric monoclonal antibody; tumor uptake; carcinoembryonic antigen; pancreatic carcinoma;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Kamigaki, T Kobe500017,Sch Med, Dept Surg 1, Chuo Ku, 7-5-2 Kusunoki Cho, Kobe, Hyogo 6 Kobe Univ 7-5-2 Kusunoki Cho Kobe Hyogo Japan 6500017 Hyogo 6
Citazione:
T. Kamigaki et al., "Enhancement of tumor uptakes by stabilized Fab homo-oligomers of a chimeric monoclonal antibody against carcinoembryonic antigen", INT J ONCOL, 14(1), 1999, pp. 139-144

Abstract

We investigated the effect of stabilized Fab oligomerization by disuccinimidyl suberate on tumor uptake in a pancreatic carcinoma xenograft model in nude mice. Recombinant mouse/human chimeric Fab of the anti-carcinoembryonic antigen (CEA) monoclonal antibody A10, which was previously shown to react specifically with gastrointestinal cancers was used in this study. Fab homo-oligomers (dimers and trimers) chemically linked with ethylene bonds (C-C oligomers) were produced by linkage of chimeric Fab. Oligomers with C-C bonds had similar immunoreactivity against human CEA to parental Fab monomer. In biodistribution studies in animals bearing pancreatic carcinoma xenografts, at 12 and 24 h after infusion, C-C oligomers showed significantly greater uptakes in tumors than Fab or F(ab')(2) but lower than IgG. However, oligomers with C-C bonds maintained higher tumor to normal tissue specificity ratios than IgG 24 h post-infusion. In conclusion, turner uptake was enhanced by Fab oligomerization with C-C bonds, compared to Fab or F(ab'),, perhaps due to the larger molecular size. It was also shown that C-C Fab oligomers could have a potency to deliver high-dose radionuclides with reduced radio-uptakes in normal tissues for the radioimmunotherapy of gastrointestinal carcinomas.

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Documento generato il 25/01/21 alle ore 14:35:15