Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1996 Aug;74(4):597–602. doi: 10.1038/bjc.1996.407

Distribution of neocarzinostatin conjugated to biotinylated chimeric monoclonal antibody Fab fragments after administration of avidin.

E Otsuji 1, T Yamaguchi 1, H Matsumura 1, K Yamamoto 1, H Tsuruta 1, Y Yata 1, H Nishi 1, K Okamoto 1, K Kitamura 1, T Takahashi 1
PMCID: PMC2074675  PMID: 8761376

Abstract

We have developed chimeric Fab fragments of MAb A7 (chA7Fab) and have reported on their potential usefulness as a carrier of neocarzinostatin (NCS). However, a large amount of chA7Fab accumulates in the kidneys which might cause renal failure. This was one of the major side-effects of the chA7Fab-NCS immunoconjugate administered to humans. To decrease the kidney accumulation of chA7Fab, chA7Fab was biotinylated and administered with a subsequent injection of avidin to nude mice with pancreatic cancer. The accumulation of biotinylated chA7Fab in the blood and the kidneys decreased significantly after the injection of avidin. In a separate experiment with biotinylated chA7Fab-NCS, the blood and kidney accumulation decreased significantly after the injection of avidin. These findings suggest that the injection of biotinylated chA7Fab complexed with NCS followed by avidin may be safer and may permit the administration of larger doses of NCS without the subsequent development of renal failure.

Full text

PDF
597

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Apelgren L. D., Zimmerman D. L., Briggs S. L., Bumol T. F. Antitumor activity of the monoclonal antibody-Vinca alkaloid immunoconjugate LY203725 (KS1/4-4-desacetylvinblastine-3-carboxhydrazide) in a nude mouse model of human ovarian cancer. Cancer Res. 1990 Jun 15;50(12):3540–3544. [PubMed] [Google Scholar]
  2. Fujita H., Nakayama N., Sawabe T., Kimura K. [In vivo distribution and inactivation of neocarzinostatin]. Jpn J Antibiot. 1970 Dec;23(5):471–478. [PubMed] [Google Scholar]
  3. GREEN N. M. AVIDIN. 1. THE USE OF (14-C)BIOTIN FOR KINETIC STUDIES AND FOR ASSAY. Biochem J. 1963 Dec;89:585–591. doi: 10.1042/bj0890585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  5. Hansson Y., Paulie S., Ben-Aïssa H., Rudberg U., Karlsson A., Perlmann P. Radioimmunolocalisation of bladder tumors xenotransplanted in nude mice. Anticancer Res. 1988 May-Jun;8(3):435–441. [PubMed] [Google Scholar]
  6. Hnatowich D. J., Virzi F., Rusckowski M. Investigations of avidin and biotin for imaging applications. J Nucl Med. 1987 Aug;28(8):1294–1302. [PubMed] [Google Scholar]
  7. Mock D. M., DuBois D. B. A sequential, solid-phase assay for biotin in physiologic fluids that correlates with expected biotin status. Anal Biochem. 1986 Mar;153(2):272–278. doi: 10.1016/0003-2697(86)90092-8. [DOI] [PubMed] [Google Scholar]
  8. Ogihara-Umeda I., Sasaki T., Toyama H., Oda K., Senda M., Nishigori H. Rapid tumor imaging by active background reduction using biotin-bearing liposomes and avidin. Cancer Res. 1994 Jan 15;54(2):463–467. [PubMed] [Google Scholar]
  9. Otsuji E., Takahashi T., Yamaguchi T., Yamaguchi N., Imanishi J. Specific cytotoxic effect of neocarzinostatin conjugated to monoclonal antibody A7 on human pancreatic carcinoma. Gastroenterol Jpn. 1990 Apr;25(2):244–248. doi: 10.1007/BF02776823. [DOI] [PubMed] [Google Scholar]
  10. Otsuji E., Yamaguchi T., Yamaoka N., Kotani T., Kato M., Taniguchi K., Kiyamura K., Takahashi T. Biodistribution of murine and chimeric Fab fragments of the monoclonal antibody A7 in human pancreatic cancer. Pancreas. 1995 Apr;10(3):265–273. doi: 10.1097/00006676-199504000-00008. [DOI] [PubMed] [Google Scholar]
  11. Otsuji E., Yamaguchi T., Yamaoka N., Taniguchi K., Kato M., Kotani T., Kitamura K., Takahashi T. Biodistribution of neocarzinostatin conjugated to chimeric Fab fragments of the monoclonal antibody A7 in nude mice bearing human pancreatic cancer xenografts. Jpn J Cancer Res. 1994 May;85(5):530–535. doi: 10.1111/j.1349-7006.1994.tb02391.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Paganelli G., Pervez S., Siccardi A. G., Rowlinson G., Deleide G., Chiolerio F., Malcovati M., Scassellati G. A., Epenetos A. A. Intraperitoneal radio-localization of tumors pre-targeted by biotinylated monoclonal antibodies. Int J Cancer. 1990 Jun 15;45(6):1184–1189. doi: 10.1002/ijc.2910450632. [DOI] [PubMed] [Google Scholar]
  13. SPIEGELBERG H. L., WEIGLE W. O. THE CATABOLISM OF HOMOLOGOUS AND HETEROLOGOUS 7S GAMMA GLOBULIN FRAGMENTS. J Exp Med. 1965 Mar 1;121:323–338. doi: 10.1084/jem.121.3.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sinitsyn V. V., Mamontova A. G., Checkneva Y. Y., Shnyra A. A., Domogatsky S. P. Rapid blood clearance of biotinylated IgG after infusion of avidin. J Nucl Med. 1989 Jan;30(1):66–69. [PubMed] [Google Scholar]
  15. Takahashi T., Yamaguchi T., Kitamura K., Noguchi A., Honda M., Otsuji E. Follow-up study of patients treated with monoclonal antibody-drug conjugate: report of 77 cases with colorectal cancer. Jpn J Cancer Res. 1993 Sep;84(9):976–981. doi: 10.1111/j.1349-7006.1993.tb00188.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Yamaguchi T., Tsurumi H., Kitamura K., Otsuji E., Miyagaki T., Kotani T., Takahashi T. Production, binding and cytotoxicity of human/mouse chimeric monoclonal antibody-neocarzinostatin conjugate. Jpn J Cancer Res. 1993 Nov;84(11):1190–1194. doi: 10.1111/j.1349-7006.1993.tb02820.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES