Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1993 Oct;68(4):684–690. doi: 10.1038/bjc.1993.410

Direct comparison of a radioiodinated intact chimeric anti-CEA MAb with its F(ab')2 fragment in nude mice bearing different human colon cancer xenografts.

C A Vogel 1, A Bischof-Delaloye 1, J P Mach 1, A Pèlegrin 1, N Hardman 1, B Delaloye 1, F Buchegger 1
PMCID: PMC1968595  PMID: 8398694

Abstract

Tumour localisation and tumour to normal tissue ratios of a chimeric anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb), in intact form and as an F(ab')2 fragment labelled with 125I and 131I, were compared in groups of nude mice bearing four different colon cancer xenografts, T380, Co112 or LoVo, of human origin, or a rat colon cancer transfected with human CEA cDNA, called '3G7'. For each tumour, three to four mice per time point were analysed 6, 12, 24, 48 and 96 h after MAb injection. In the different tumours, maximal localisation of intact MAb was obtained at 24 to 48 h, and of F(ab')2 fragment 12 to 24 h after injection. Among the different tumours, localisation was highest with colon cancer T380, with 64% of the injected dose per gram (% ID/g) for the intact MAb and 57% for its F(ab')2 fragment, while in the three other tumours, maximal localisation ranged from 14 to 22% ID g-1 for the intact MAb and was about 11% for the F(ab')2. Tumour to normal tissue ratios of intact MAb increased rapidly until 24 h after injection and remained stable or showed only a minor increase thereafter. In contrast, for the F(ab')2 fragment, the tumour to normal tissue ratios increased steadily up to 4 days after injection reaching markedly higher values than those obtained with intact MAb. For the four different xenografts, tumour to blood ratios of F(ab')2 were about 2, 3 and 5 to 16 times higher than those of intact antibodies at 12, 24 and 96 h after injection, respectively.

Full text

PDF
690

Selected References

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

  1. Audette M., Buchegger F., Schreyer M., Mach J. P. Monoclonal antibody against carcinoembryonic antigen (CEA) identifies two new forms of crossreacting antigens of molecular weight 90,000 and 160,000 in normal granulocytes. Mol Immunol. 1987 Nov;24(11):1177–1186. doi: 10.1016/0161-5890(87)90164-7. [DOI] [PubMed] [Google Scholar]
  2. Bagshawe K. D. Antibody-directed enzyme/prodrug therapy (ADEPT). Biochem Soc Trans. 1990 Oct;18(5):750–752. doi: 10.1042/bst0180750. [DOI] [PubMed] [Google Scholar]
  3. Bischof-Delaloye A., Delaloye B., Buchegger F., Gilgien W., Studer A., Curchod S., Givel J. C., Mosimann F., Pettavel J., Mach J. P. Clinical value of immunoscintigraphy in colorectal carcinoma patients: a prospective study. J Nucl Med. 1989 Oct;30(10):1646–1656. [PubMed] [Google Scholar]
  4. Breitz H. B., Weiden P. L., Vanderheyden J. L., Appelbaum J. W., Bjorn M. J., Fer M. F., Wolf S. B., Ratliff B. A., Seiler C. A., Foisie D. C. Clinical experience with rhenium-186-labeled monoclonal antibodies for radioimmunotherapy: results of phase I trials. J Nucl Med. 1992 Jun;33(6):1099–1109. [PubMed] [Google Scholar]
  5. Buchegger F., Chalandon Y., Pèlegrin A., Hardman N., Mach J. P. Bone marrow dosimetry in rats using direct tissue counting after injection of radio-iodinated intact monoclonal antibodies or F(ab')2 fragments. J Nucl Med. 1991 Jul;32(7):1414–1421. [PubMed] [Google Scholar]
  6. Buchegger F., Haskell C. M., Schreyer M., Scazziga B. R., Randin S., Carrel S., Mach J. P. Radiolabeled fragments of monoclonal antibodies against carcinoembryonic antigen for localization of human colon carcinoma grafted into nude mice. J Exp Med. 1983 Aug 1;158(2):413–427. doi: 10.1084/jem.158.2.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Buchegger F., Pfister C., Fournier K., Prevel F., Schreyer M., Carrel S., Mach J. P. Ablation of human colon carcinoma in nude mice by 131I-labeled monoclonal anti-carcinoembryonic antigen antibody F(ab')2 fragments. J Clin Invest. 1989 May;83(5):1449–1456. doi: 10.1172/JCI114037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Buchegger F., Pèlegrin A., Delaloye B., Bischof-Delaloye A., Mach J. P. Iodine-131-labeled MAb F(ab')2 fragments are more efficient and less toxic than intact anti-CEA antibodies in radioimmunotherapy of large human colon carcinoma grafted in nude mice. J Nucl Med. 1990 Jun;31(6):1035–1044. [PubMed] [Google Scholar]
  9. Buchegger F., Pèlegrin A., Hardman N., Heusser C., Lukas J., Dolci W., Mach J. P. Different behaviour of mouse-human chimeric antibody F(ab')2 fragments of IgG1, IgG2 and IgG4 sub-class in vivo. Int J Cancer. 1992 Feb 1;50(3):416–422. doi: 10.1002/ijc.2910500316. [DOI] [PubMed] [Google Scholar]
  10. Buchegger F., Schreyer M., Carrel S., Mach J. P. Monoclonal antibodies identify a CEA crossreacting antigen of 95 kD (NCA-95) distinct in antigenicity and tissue distribution from the previously described NCA of 55 kD. Int J Cancer. 1984 May 15;33(5):643–649. doi: 10.1002/ijc.2910330515. [DOI] [PubMed] [Google Scholar]
  11. Cheung N. K., Landmeier B., Neely J., Nelson A. D., Abramowsky C., Ellery S., Adams R. B., Miraldi F. Complete tumor ablation with iodine 131-radiolabeled disialoganglioside GD2-specific monoclonal antibody against human neuroblastoma xenografted in nude mice. J Natl Cancer Inst. 1986 Sep;77(3):739–745. doi: 10.1093/jnci/77.3.739. [DOI] [PubMed] [Google Scholar]
  12. Colcher D., Zalutsky M., Kaplan W., Kufe D., Austin F., Schlom J. Radiolocalization of human mammary tumors in athymic mice by a monoclonal antibody. Cancer Res. 1983 Feb;43(2):736–742. [PubMed] [Google Scholar]
  13. Drewinko B., Romsdahl M. M., Yang L. Y., Ahearn M. J., Trujillo J. M. Establishment of a human carcinoembryonic antigen-producing colon adenocarcinoma cell line. Cancer Res. 1976 Feb;36(2 Pt 1):467–475. [PubMed] [Google Scholar]
  14. Folli S., Pèlegrin A., Chalandon Y., Yao X., Buchegger F., Lienard D., Lejeune F., Mach J. P. Tumor-necrosis factor can enhance radio-antibody uptake in human colon carcinoma xenografts by increasing vascular permeability. Int J Cancer. 1993 Mar 12;53(5):829–836. doi: 10.1002/ijc.2910530521. [DOI] [PubMed] [Google Scholar]
  15. Goodwin D. A., Meares C. F., McCall M. J., McTigue M., Chaovapong W. Pre-targeted immunoscintigraphy of murine tumors with indium-111-labeled bifunctional haptens. J Nucl Med. 1988 Feb;29(2):226–234. [PubMed] [Google Scholar]
  16. Hammarstrom S., Shively J. E., Paxton R. J., Beatty B. G., Larsson A., Ghosh R., Bormer O., Buchegger F., Mach J. P., Burtin P. Antigenic sites in carcinoembryonic antigen. Cancer Res. 1989 Sep 1;49(17):4852–4858. [PubMed] [Google Scholar]
  17. Hardman N., Gill L. L., De Winter R. F., Wagner K., Hollis M., Businger F., Ammaturo D., Buchegger F., Mach J. P., Heusser C. Generation of a recombinant mouse-human chimaeric monoclonal antibody directed against human carcinoembryonic antigen. Int J Cancer. 1989 Sep 15;44(3):424–433. doi: 10.1002/ijc.2910440308. [DOI] [PubMed] [Google Scholar]
  18. Herlyn D., Powe J., Alavi A., Mattis J. A., Herlyn M., Ernst C., Vaum R., Koprowski H. Radioimmunodetection of human tumor xenografts by monoclonal antibodies. Cancer Res. 1983 Jun;43(6):2731–2735. [PubMed] [Google Scholar]
  19. Lamoyi E., Nisonoff A. Preparation of F(ab')2 fragments from mouse IgG of various subclasses. J Immunol Methods. 1983 Jan 28;56(2):235–243. doi: 10.1016/0022-1759(83)90415-5. [DOI] [PubMed] [Google Scholar]
  20. Le Doussal J. M., Gruaz-Guyon A., Martin M., Gautherot E., Delaage M., Barbet J. Targeting of indium 111-labeled bivalent hapten to human melanoma mediated by bispecific monoclonal antibody conjugates: imaging of tumors hosted in nude mice. Cancer Res. 1990 Jun 1;50(11):3445–3452. [PubMed] [Google Scholar]
  21. Le Doussal J. M., Martin M., Gautherot E., Delaage M., Barbet J. In vitro and in vivo targeting of radiolabeled monovalent and divalent haptens with dual specificity monoclonal antibody conjugates: enhanced divalent hapten affinity for cell-bound antibody conjugate. J Nucl Med. 1989 Aug;30(8):1358–1366. [PubMed] [Google Scholar]
  22. Mach J. P., Carrel S., Merenda C., Sordat B., Cerottini J. C. In vivo localisation of radiolabelled antibodies to carcinoembryonic antigen in human colon carcinoma grafted into nude mice. Nature. 1974 Apr 19;248(5450):704–706. doi: 10.1038/248704a0. [DOI] [PubMed] [Google Scholar]
  23. Martin K. W., Halpern S. E. Carcinoembryonic antigen production, secretion, and kinetics in BALB/c mice and a nude mouse-human tumor model. Cancer Res. 1984 Dec;44(12 Pt 1):5475–5481. [PubMed] [Google Scholar]
  24. Milenic D. E., Yokota T., Filpula D. R., Finkelman M. A., Dodd S. W., Wood J. F., Whitlow M., Snoy P., Schlom J. Construction, binding properties, metabolism, and tumor targeting of a single-chain Fv derived from the pancarcinoma monoclonal antibody CC49. Cancer Res. 1991 Dec 1;51(23 Pt 1):6363–6371. [PubMed] [Google Scholar]
  25. PRESSMAN D., DAY E. D., BLAU M. The use of paired labeling in the determination of tumor-localizing antibodies. Cancer Res. 1957 Oct;17(9):845–850. [PubMed] [Google Scholar]
  26. Pervez S., Paganelli G., Epenetos A. A., Mooi W. J., Evans D. J., Krausz T. Localization of biotinylated monoclonal antibody in nude mice bearing subcutaneous and intraperitoneal human tumour xenografts. Int J Cancer Suppl. 1988;3:30–33. doi: 10.1002/ijc.2910410807. [DOI] [PubMed] [Google Scholar]
  27. Press O. W., Eary J. F., Badger C. C., Martin P. J., Appelbaum F. R., Levy R., Miller R., Brown S., Nelp W. B., Krohn K. A. Treatment of refractory non-Hodgkin's lymphoma with radiolabeled MB-1 (anti-CD37) antibody. J Clin Oncol. 1989 Aug;7(8):1027–1038. doi: 10.1200/JCO.1989.7.8.1027. [DOI] [PubMed] [Google Scholar]
  28. Pèlegrin A., Terskikh A., Hayoz D., Chalandon Y., Olsson N. O., Folli S., Buchegger F., Kromer B., Schwarz K., Martin M. Human carcinoembryonic antigen cDNA expressed in rat carcinoma cells can function as target antigen for tumor localization of antibodies in nude rats and as rejection antigen in syngeneic rats. Int J Cancer. 1992 Aug 19;52(1):110–119. doi: 10.1002/ijc.2910520120. [DOI] [PubMed] [Google Scholar]
  29. Senekowitsch R., Reidel G., Möllenstädt S., Kriegel H., Pabst H. W. Curative radioimmunotherapy of human mammary carcinoma xenografts with iodine-131-labeled monoclonal antibodies. J Nucl Med. 1989 Apr;30(4):531–537. [PubMed] [Google Scholar]
  30. Wahl R. L., Parker C. W., Philpott G. W. Improved radioimaging and tumor localization with monoclonal F(ab')2. J Nucl Med. 1983 Apr;24(4):316–325. [PubMed] [Google Scholar]

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

RESOURCES