Abstract
A mouse monoclonal anti-CEA antibody (11.285.14) has been examined for tumour localization potential by assessing its distribution in immunodeprived mice with xenografts of human colon carcinoma cell lines HCT-8, HRT-18, HT-29, and LS174T and a xenograft (HRVB) established from a primary rectal carcinoma. With four carcinomas (HCT-8, HT-29, LS174T, and HRVB) preferential tumour localization of 125I anti-CEA was seen. Compared with 131I normal IgG1 localization indices of up to 4.4:1 were achieved. Up to 10% of the injected dose of 125I anti-CEA was present/g of tumour tissue and with the largest xenografts examined (3–4 g) up to 40% of the total body reactivity was localized in tumour tissue. The tumour localization of 131I labelled antibody was visualized by external gamma camera imaging. Overall antibody localization correlated with the CEA content of the xenografts and the fourth colon carcinoma xenograft (HRT-18) and an osteogenic sarcoma xenograft (791T), both with very low CEA levels, showed no localization of the monoclonal antibody.
Keywords: Colon Carcinoma Cell Line, Human Colon Carcinoma Cell, Carcinoma Xenograft, Human Colon Carcinoma Cell Line, Gamma Camera Imaging
References
- 1.Berche C, Mach J-P, Lumbroso J-D, Langlais C, Aubry F, Buchegger F, Carrel S, Rougier P, Parmentier C, Tubiana M. Tomoscintigraphy for detecting gastrointestinal and medullary thyroid cancers: First clinical results using radiolabelled monoclonal antibodies against carcinoembryonic antigen. Br Med J. 1982;285:1447. doi: 10.1136/bmj.285.6353.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Buchegger F, Haskell CM, Schreyer M, Scazziga BR, Randin S, Carrel S, Mach J-P. Radiolabelled fragments of monoclonal antibodies against carcinoembryonic antigen for localization of human colon carcinoma grafted into nude mice. J Exp Med. 1983;158:413. doi: 10.1084/jem.158.2.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Corvalan JRF, Axton CA, Brandon DR, Smith W, Woodhouse Classification of anti-CEA monoclonal antibodies. Protides of the Biol Fluids. 1984;31:921. [Google Scholar]
- 4.Gaffar SA, Pant KD, Scochat D, Bennett SJ, Goldenberg DM. Experimental studies of tumour radioimmunodetection using antibody mixture against carcinoembryonic antigen (CEA) and colon specific antigen-p (CSAP) Int J Cancer. 1981;27:101. doi: 10.1002/ijc.2910270116. [DOI] [PubMed] [Google Scholar]
- 5.Gatter KC, Abdulaziz Z, Beverley P, Corvalan JRF, Ford C, Lane EB, Mota M, Nash JRG, Pulford K, Stein H, Taylor-Papadimitriou J, Woodhouse C, Mason DY. Use of monoclonal antibodies for the histopathological diagnosis of human malignancy. J Clin Path. 1982;35:1253. doi: 10.1136/jcp.35.11.1253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Ghose T, Ferrone S, Imai K, Norvell ST, Luner SJ, Martin RH, Blair AH. Imaging of human melanoma xenografts in nude mice with radiolabelled monoclonal antibody. J Natl Cancer Inst. 1982;69:823. [PubMed] [Google Scholar]
- 7.Haskell LM, Buchegger F, Schreyer M, Carrel S, Mach J-P. Monoclonal antibodies to carcinoembryonic antigen: Ionic strength as a factor in the selection of antibodies for immunoscintigraphy. Cancer Res. 1983;43:3857. [PubMed] [Google Scholar]
- 8.Hedin A, Wahren B, Hammarstrom S. Tumor localization of CEA-containing human tumors in nude mice by means of monoclonal anti-CEA antibodies. Int J Cancer. 1982;30:547. doi: 10.1002/ijc.2910300503. [DOI] [PubMed] [Google Scholar]
- 9.Hedin A, Hammarstrom S, Larson A. Specifities and binding properties of eight monoclonal antibodies against carcinoembryonic antigen. Mol Immunol. 1982;19:1641. doi: 10.1016/0161-5890(82)90275-9. [DOI] [PubMed] [Google Scholar]
- 10.Hockey M, Ford C, Newman C, Corvalan JRF, Rowland GF, Stokes H, Thompson H, Fielding JWL. The immunohistochemical localisation of carcinoembryonic antigen (CEA) with monoclonal antibody in gastric adenocarcinomas. Br J Surg. 1983;70:300. [Google Scholar]
- 11.Larson SM, Brown JP, Wright PW, Carrasquillo JA, Hellstrom I, Hellstrom KE. Imaging of melanoma with I131-labelled monoclonal antibodies. J Nucl Med. 1982;24:123. [PubMed] [Google Scholar]
- 12.Levine G, Ballou B, Reiland J, Solter D, Gumerman L, Hakala T. Localization of I131-labelled tumor specific monoclonal antibody in the tumour bearing Balb/c mouse. J Nucl Med. 1980;21:570. [PubMed] [Google Scholar]
- 13.Mach J-P, Buchegger F, Forni M, Ritschard J, Berche C, Lumbroso J-D, Schreyer M, Giradet C, Accolla RS, Carrel S. Use of radiolabelled monoclonal anti-CEA antibodies for the detection of human carcinomas by external photoscanning and tomoscintigraphy. Immunol Today. 1981;2:239. doi: 10.1016/0167-5699(81)90011-6. [DOI] [PubMed] [Google Scholar]
- 14.Moshakis V, McIlhinney RAJ, Raghavan D, Neville AM. Localization of human tumour xenografts after IV administration of radiolabelled monoclonal antibodies. Br J Cancer. 1981;44:91. doi: 10.1038/bjc.1981.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Pimm MV, Baldwin RW. Quantitative evaluation of the localization of a monoclonal antibody (791T/36) in human osteogenic sarcoma xenografts. Eur J Cancer Clin Oncol. 1984;20:315. doi: 10.1016/0277-5379(84)90238-4. [DOI] [PubMed] [Google Scholar]
- 16.Pimm MV, Embleton MJ, Perkins AC, Price MR, Robins RA, Robinson GR, Baldwin RW. In vivo localization of anti-osteogenic sarcoma 791T monoclonal antibody in osteogenic sarcoma xenografts. Int J Cancer. 1982;30:75. doi: 10.1002/ijc.2910300114. [DOI] [PubMed] [Google Scholar]
- 17.Primus FJ, Newell KD, Blue A, Goldenberg DM. Immunological heterogeneity of carcinoembryonic antigen distinguished by monoclonal antibodies. Cancer Res. 1983;43:686. [PubMed] [Google Scholar]
- 18.Rainsbury R, Westwood J. Tumour localization with monoclonal antibody radioactively labelled with metal chelate rather than iodine. Lancet. 1982;2:1347. doi: 10.1016/s0140-6736(82)91553-7. [DOI] [PubMed] [Google Scholar]
- 19.Rowland GF, Corvalan JRF, Axton CA, Gore VA, Marsden CH, Smith W, Simmonds RG. Suppression of growth of a human colo-rectal tumour in nude mice by vindesine-monoclonal anti-CEA conjugates. Protides of the Biological Fluids. 1984;31:783. [Google Scholar]
- 20.Simmonds RG, Smith W, Corvalan JRF. Affinity purification of anti-CEA antibody. Protides of the Biological Fluids. 1984;31:917. [Google Scholar]
- 21.Steel GG, Courtney VD, Rostrom RY. Improved immune suppression techniques for the xenografting of human tumours. Br J Cancer. 1978;37:224. doi: 10.1038/bjc.1978.30. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Wagener C, Petzold P, Kohler W, Totovic V. Binding of five monoclonal anti-CEA antibodies with different epitope specificities to various carcinoma tissues. Int J Cancer. 1984;33:469. doi: 10.1002/ijc.2910330409. [DOI] [PubMed] [Google Scholar]