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. 1997;75(7):1049–1060. doi: 10.1038/bjc.1997.179

Selection of monoclonal antibody E48 IgG or U36 IgG for adjuvant radioimmunotherapy in head and neck cancer patients.

R de Bree 1, J C Roos 1, M A Plaizier 1, J J Quak 1, G J van Kamp 1, W den Hollander 1, G B Snow 1, G A van Dongen 1
PMCID: PMC2222739  PMID: 9083342

Abstract

Preliminary data from recent clinical radioimmunoscintigraphy studies indicate that 99mTc-labelled murine monoclonal antibodies (MAbs) E48 and U36 have a similar ability to target squamous cell carcinoma of the head and neck (HNSCC) selectively. In the present study we describe additional aspects of murine and chimeric MAb (mMAb and cMAb) E48 and U36, which might influence the selection of one MAb for adjuvant radioimmunotherapy. To make direct comparison possible, ten patients received 11.2 +/- 0.3 and 11.1 +/- 0.2 mg (n = 5) or 51.1 +/- 0.1 and 51.0 +/- 0.4 mg (n = 5) of both mE48 IgG and mU36 IgG labelled with 131I and 125I simultaneously and underwent surgery 7-8 days after injection. The mean uptake of iodine-labelled mE48 IgG and mU36 was highest in tumour tissue, 8.9 +/- 8.9 and 8.2 +/- 4.4 %ID kg(-1) respectively. Tumour to non-tumour ratios for oral mucosa, skin, muscle, blood and bone marrow aspirate were 2.5, 5.5, 25.2, 4.7 and 4.0 respectively in the case of mE48 IgG and 2.3, 4.1, 21.0, 5.8 and 5.8 respectively in the case of mU36 IgG. The distribution of mMAbs E48 and U36 throughout tumours that had been collected in previous studies was heterogeneous when administered at a dose of 1 or 12 mg, and homogeneous when administered at a dose of 52 mg. Administration of mE48 IgG (1-52 mg) resulted in a human anti-mouse antibody response in 12 out of 28 patients, while for mU36 IgG (1-52 mg), this figure was three out of 18 patients. cMAb E48 was shown to be highly effective in mediating antibody-dependent cellular cytotoxicity in vitro, while cMAb U36 and mMAbs E48 and U36 were not effective at all. Rationales are provided that give priority to the start of adjuvant radioimmunotherapy trials with 186Re-labelled cMAb U36 IgG in head and neck cancer patients who are at high risk for the development of locoregional recurrences and distant metastases.

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Selected References

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

  1. Blumenthal R. D., Fand I., Sharkey R. M., Boerman O. C., Kashi R., Goldenberg D. M. The effect of antibody protein dose on the uniformity of tumor distribution of radioantibodies: an autoradiographic study. Cancer Immunol Immunother. 1991;33(6):351–358. doi: 10.1007/BF01741594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brakenhoff R. H., van Gog F. B., Looney J. E., van Walsum M., Snow G. B., van Dongen G. A. Construction and characterization of the chimeric monoclonal antibody E48 for therapy of head and neck cancer. Cancer Immunol Immunother. 1995 Mar;40(3):191–200. doi: 10.1007/BF01517351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Buist M. R., Kenemans P., Molthoff C. F., Roos J. C., Den Hollander W., Brinkhuis M., Baak J. P. Tumor uptake of intravenously administered radiolabeled antibodies in ovarian carcinoma patients in relation to antigen expression and other tumor characteristics. Int J Cancer. 1995 Apr 21;64(2):92–98. doi: 10.1002/ijc.2910640204. [DOI] [PubMed] [Google Scholar]
  5. Buist M. R., Kenemans P., van Kamp G. J., Haisma H. J. Minor human antibody response to a mouse and chimeric monoclonal antibody after a single i.v. infusion in ovarian carcinoma patients: a comparison of five assays. Cancer Immunol Immunother. 1995 Jan;40(1):24–30. doi: 10.1007/BF01517232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Crippa F., Bolis G., Seregni E., Gavoni N., Scarfone G., Ferraris C., Buraggi G. L., Bombardieri E. Single-dose intraperitoneal radioimmunotherapy with the murine monoclonal antibody I-131 MOv18: clinical results in patients with minimal residual disease of ovarian cancer. Eur J Cancer. 1995;31A(5):686–690. doi: 10.1016/0959-8049(94)00454-d. [DOI] [PubMed] [Google Scholar]
  7. De Bree R., Roos J. C., Quak J. J., Den Hollander W., Snow G. B., Van Dongen G. A. Clinical screening of monoclonal antibodies 323/A3, cSF-25 and K928 for suitability of targetting tumours in the upper aerodigestive and respiratory tract. Nucl Med Commun. 1994 Aug;15(8):613–627. doi: 10.1097/00006231-199408000-00006. [DOI] [PubMed] [Google Scholar]
  8. Gerretsen M., Visser G. W., Brakenhoff R. H., van Walsum M., Snow G. B., van Dongen G. A. Complete ablation of small squamous cell carcinoma xenografts with 186Re-labeled monoclonal antibody E48. Cell Biophys. 1994;24-25:135–142. doi: 10.1007/BF02789224. [DOI] [PubMed] [Google Scholar]
  9. Gerretsen M., Visser G. W., van Walsum M., Meijer C. J., Snow G. B., van Dongen G. A. 186Re-labeled monoclonal antibody E48 immunoglobulin G-mediated therapy of human head and neck squamous cell carcinoma xenografts. Cancer Res. 1993 Aug 1;53(15):3524–3529. [PubMed] [Google Scholar]
  10. Goldenberg D. M. Future role of radiolabeled monoclonal antibodies in oncological diagnosis and therapy. Semin Nucl Med. 1989 Oct;19(4):332–339. doi: 10.1016/s0001-2998(89)80025-x. [DOI] [PubMed] [Google Scholar]
  11. Jacobs A. J., Fer M., Su F. M., Breitz H., Thompson J., Goodgold H., Cain J., Heaps J., Weiden P. A phase I trial of a rhenium 186-labeled monoclonal antibody administered intraperitoneally in ovarian carcinoma: toxicity and clinical response. Obstet Gynecol. 1993 Oct;82(4 Pt 1):586–593. [PubMed] [Google Scholar]
  12. Khazaeli M. B., Conry R. M., LoBuglio A. F. Human immune response to monoclonal antibodies. J Immunother Emphasis Tumor Immunol. 1994 Jan;15(1):42–52. doi: 10.1097/00002371-199401000-00006. [DOI] [PubMed] [Google Scholar]
  13. Oosterwijk E., Bander N. H., Divgi C. R., Welt S., Wakka J. C., Finn R. D., Carswell E. A., Larson S. M., Warnaar S. O., Fleuren G. J. Antibody localization in human renal cell carcinoma: a phase I study of monoclonal antibody G250. J Clin Oncol. 1993 Apr;11(4):738–750. doi: 10.1200/JCO.1993.11.4.738. [DOI] [PubMed] [Google Scholar]
  14. Parker S. L., Tong T., Bolden S., Wingo P. A. Cancer statistics, 1996. CA Cancer J Clin. 1996 Jan-Feb;46(1):5–27. doi: 10.3322/canjclin.46.1.5. [DOI] [PubMed] [Google Scholar]
  15. Quak J. J., Balm A. J., van Dongen G. A., Brakkee J. G., Scheper R. J., Snow G. B., Meijer C. J. A 22-kd surface antigen detected by monoclonal antibody E 48 is exclusively expressed in stratified squamous and transitional epithelia. Am J Pathol. 1990 Jan;136(1):191–197. [PMC free article] [PubMed] [Google Scholar]
  16. Riethmüller G., Schneider-Gädicke E., Schlimok G., Schmiegel W., Raab R., Höffken K., Gruber R., Pichlmaier H., Hirche H., Pichlmayr R. Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma. German Cancer Aid 17-1A Study Group. Lancet. 1994 May 14;343(8907):1177–1183. doi: 10.1016/s0140-6736(94)92398-1. [DOI] [PubMed] [Google Scholar]
  17. Schrijvers A. H., Quak J. J., Uyterlinde A. M., van Walsum M., Meijer C. J., Snow G. B., van Dongen G. A. MAb U36, a novel monoclonal antibody successful in immunotargeting of squamous cell carcinoma of the head and neck. Cancer Res. 1993 Sep 15;53(18):4383–4390. [PubMed] [Google Scholar]
  18. Stell P. M., Rawson N. S. Adjuvant chemotherapy in head and neck cancer. Br J Cancer. 1990 May;61(5):779–787. doi: 10.1038/bjc.1990.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Steplewski Z., Sun L. K., Shearman C. W., Ghrayeb J., Daddona P., Koprowski H. Biological activity of human-mouse IgG1, IgG2, IgG3, and IgG4 chimeric monoclonal antibodies with antitumor specificity. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4852–4856. doi: 10.1073/pnas.85.13.4852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Stupp R., Weichselbaum R. R., Vokes E. E. Combined modality therapy of head and neck cancer. Semin Oncol. 1994 Jun;21(3):349–358. [PubMed] [Google Scholar]
  21. Takahashi H., Wilson B., Ozturk M., Motté P., Strauss W., Isselbacher K. J., Wands J. R. In vivo localization of human colon adenocarcinoma by monoclonal antibody binding to a highly expressed cell surface antigen. Cancer Res. 1988 Nov 15;48(22):6573–6579. [PubMed] [Google Scholar]
  22. Van Hal N. L., Van Dongen G. A., Rood-Knippels E. M., Van Der Valk P., Snow G. B., Brakenhoff R. H. Monoclonal antibody U36, a suitable candidate for clinical immunotherapy of squamous-cell carcinoma, recognizes a CD44 isoform. Int J Cancer. 1996 Nov 15;68(4):520–527. doi: 10.1002/(SICI)1097-0215(19961115)68:4<520::AID-IJC19>3.0.CO;2-8. [DOI] [PubMed] [Google Scholar]
  23. Vernham G. A., Crowther J. A. Head and neck carcinoma--stage at presentation. Clin Otolaryngol Allied Sci. 1994 Apr;19(2):120–124. doi: 10.1111/j.1365-2273.1994.tb01194.x. [DOI] [PubMed] [Google Scholar]
  24. de Bree R., Roos J. C., Quak J. J., den Hollander W., Snow G. B., van Dongen G. A. Radioimmunoscintigraphy and biodistribution of technetium-99m-labeled monoclonal antibody U36 in patients with head and neck cancer. Clin Cancer Res. 1995 Jun;1(6):591–598. [PubMed] [Google Scholar]
  25. de Bree R., Roos J. C., Quak J. J., den Hollander W., van den Brekel M. W., van der Wal J. E., Tobi H., Snow G. B., van Dongen G. A. Clinical imaging of head and neck cancer with technetium-99m-labeled monoclonal antibody E48 IgG or F(ab')2. J Nucl Med. 1994 May;35(5):775–783. [PubMed] [Google Scholar]
  26. van Gog F. B., Visser G. W., Klok R., van der Schors R., Snow G. B., van Dongen G. A. Monoclonal antibodies labeled with rhenium-186 using the MAG3 chelate: relationship between the number of chelated groups and biodistribution characteristics. J Nucl Med. 1996 Feb;37(2):352–362. [PubMed] [Google Scholar]

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