Europe PMC

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

Abstract 


The MC-38 C57BL/6 mouse colon adenocarcinoma cell line has been transduced with a retroviral construct containing cDNA encoding the human carcinoembryonic antigen (CEA) gene [Robbins PF, Kantor JA, Salgaller M, Horan Hand P, Fernsten PD, Schlom J (1991) Cancer Res 51: 3657]. Two clones, MC-38-ceal and MC-38-cea2, expressed high levels of CEA on their cell surface. A third CEA-expressing cell line, MCA-102-cea3, was similarly derived by transduction of the MCA-102 C57BL/6 mouse fibrosarcoma cell line and is described here. In this study, the three CEA-transduced murine tumor cell lines (MC-38-ceal, MC-38-cea2, MCA-102-cea3) were evaluated for their tumorigenic potential, as well as their ability to serve as in vivo model systems for active and passive immunotherapy studies. Parameters that were investigated include tumor growth rate, the antibody response of the host to CEA, and the CEA content of the tumors. The MC-38-cea2 model appeared to be the most appropriate for immunotherapy studies. Biodistribution studies, using an 125I-labeled anti-CEA mAb, demonstrated efficient tumor targeting of MC-38-cea2 tumors in C57BL/6 and athymic mice.

Free full text 


Logo of ciiLink to Publisher's site
Cancer Immunol Immunother. 1993 Mar; 36(2): 65–75.
PMCID: PMC11037972
PMID: 8425211

Evaluation of human carcinoembryonic-antigen (CEA)-transduced and non-transduced murine tumors as potential targets for anti-CEA therapies

Abstract

The MC-38 C57BL/6 mouse colon adenocarcinoma cell line has been transduced with a retroviral construct containing cDNA encoding the human carcinoembryonic antigen (CEA) gene [Robbins PF, Kantor JA, Salgaller M, Horan Hand P, Fernsten PD, Schlom J (1991) Cancer Res 51: 3657]. Two clones, MC-38-ceal and MC-38-cea2, expressed high levels of CEA on their cell surface. A third CEA-expressing cell line, MCA-102-cea3, was similarly derived by transduction of the MCA-102 C57BL/6 mouse fibrosarcoma cell line and is described here. In this study, the three CEA-transduced murine tumor cell lines (MC-38-cea1, MC-38-cea2, MCA-102-cea3) were evaluated for their tumorigenic potential, as well as their ability to serve as in vivo model systems for active and passive immunotherapy studies. Parameters that were investigated include tumor growth rate, the antibody response of the host to CEA, and the CEA content of the tumors. The MC-38-cea2 model appeared to be the most appropriate for immunotherapy studies. Biodistribution studies, using an125I-labeled anti-CEA mAb, demonstrated efficient tumor targeting of MC-38-cea2 tumors in C57BL/6 and athymic mice.

Key words: Carcinoembryonic antigen, Immunotherapy, CEA-transduced tumor cells

References

1. Barnett TR, Kretschmer A, Austen DA, Goebel SJ. Carcinoembryonic antigens: alternative splicing accounts for the multiple mRNAs that code for novel members of the carcinoembryonic antigen family. J Cell Biol. 1989;108:267–267. [Europe PMC free article] [Abstract] [Google Scholar]
2. Bast RC, Jr, Feeney M, Lazarus H, et al. Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest. 1981;68:1331–1331. [Europe PMC free article] [Abstract] [Google Scholar]
3. Beauchemin N, Benchimol S, Cournoyer D, Fuks A, Stanners CP. Isolation and characterization of full-length functional cDNA clones for human carcinoembryonic antigen. Mol Cell Biol. 1987;7:3221–3221. [Europe PMC free article] [Abstract] [Google Scholar]
4. Benchimol S, Fuks A, Jothy S, Beachemin N, Shirota K, Stanners CP. Carcinoembryonic antigen, a human tumor marker, functions as an intracellular adhesion molecule. Cell. 1989;57:327–327. [Abstract] [Google Scholar]
5. 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;43:736–736. [Abstract] [Google Scholar]
6. Colcher D, Milenic D, Roselli M, Raubitschek A, Yarranton G, King D, Adair J, Whittle N, Bodmer M, Schlom J. Characterization and biodistribution of recombinant and recombinant/chimeric constructs of monoclonal antibody B72.3. Cancer Res. 1989;49:1738–1738. [Abstract] [Google Scholar]
7. Estin CD, Stevenson US, Plowman GD, Hu S-L, Sridhar P, Hellstrom I, Brown JP, Hellstrom KE. Recombinant vaccinia virus vaccine against the human melanoma antigen p97 for use in immunotherapy. Proc Natl Acad Sci USA. 1988;85:1052–1052. [Europe PMC free article] [Abstract] [Google Scholar]
8. Fox BA, Spiess PF, Kasid A, Puri R, Mule JJ, Weber JS, Rosenberg SA. In vitro and in vivo antitumor properties of a T-cell clone generated from murine tumor-infiltrating lymphocytes. J Biol Response Mod. 1990;9:499–499. [Abstract] [Google Scholar]
9. Gold P, Freedman SO. Specific carcinoembryonic antigens of the human digestive system. J Exp Med. 1965;122:467–467. [Europe PMC free article] [Abstract] [Google Scholar]
10. Guadagni F, Witt PL, Robbins PF, Schlom J, Greiner JW. Regulation of carcinoembryonic antigen expression in different human colorectal tumor cells by interferon-gamma. Cancer Res. 1990;50:6248–6248. [Abstract] [Google Scholar]
11. Guesdon JL, Terynck T, Avrameas S. The use of avidin-biotin interaction in immunoenzymatic techniques. J Histochem Cytochem. 1979;27:1131–1131. [Abstract] [Google Scholar]
12. Hostetter RB, Augustus LB, Mankarious R, Chi K, Fan D, Toth C, Thomas P, Jessup JM. Carcinoembryonic antigen as a selective enhancer of colorectal cancer metastasis. J Natl Cancer Inst. 1990;82:380–380. [Abstract] [Google Scholar]
13. Johnson VG, Schlom J, Paterson AJ, Bennett J, Magnani JL, Colcher D. Analysis of a human tumor-associated glycoprotein (TAG-72) identified by monoclonal antibody B72.3. Cancer Res. 1986;46:850–850. [Abstract] [Google Scholar]
14. Kantor J, Irvine K, Abrams S, Kaufmann H, DiPietro J, Schlom J. Anti-tumor activity and immune responses induced by a recombinant vaccinia-carcinoembryonic antigen (CEA) vaccine. J Natl Cancer Inst. 1992;84:1084–1084. [Abstract] [Google Scholar]
15. Kaufman H, Schlom J, Kantor J. A recombinant vaccinia virus expressing human carcinoembryonic antigen (CEA) Int J Cancer. 1991;48:900–900. [Abstract] [Google Scholar]
16. Koprowski H, Steplewski Z, Mitchell K, Herlyn M. Colorectal carcinoma antigens detected by hybridoma antibodies. Somat Cell Genet. 1979;5:957–957. [Abstract] [Google Scholar]
17. Kufe D, Inghirami G, Abe M, Hayes D. Differential reactivity of a novel monoclonal antibody (DF3) with human malignant versus benign breast tumors. Hybridoma. 1984;3:223–223. [Abstract] [Google Scholar]
18. Lafreniere R, Rosenberg SA. A novel approach to the generation and identification of experimental hepatic metastases in a murine model. J Natl Cancer Inst. 1986;76:309–309. [Abstract] [Google Scholar]
19. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265–265. [Abstract] [Google Scholar]
20. Mann R, Mulligan RC, Baltimore D. Construction of a retrovirus packaging mutant and its use to produce a helper-free defective retrovirus. Cell. 1983;33:153–153. [Abstract] [Google Scholar]
21. Muraro R, Wunderlich D, Thor A, Lundy J, Noguchi P, Cunningham R, Schlom J. Definition by monoclonal antibodies of a repertoire of epitopes on carcinoembryonic antigen differentially expressed in human colon carcinomas versus normal adult tissues. Cancer Res. 1985;45:5769–5769. [Abstract] [Google Scholar]
22. Noguchi P, Wallace R, Johnson J, Early E, O'Brien S, Ferrone S, Pellegrino MA, Milstein J, Needy C, Browne W, Petricciani J. Characterization of WiDr: a human colon carcinoma cell line. In Vitro (Rockville) 1979;15:401–401. [Abstract] [Google Scholar]
23. Oikawa S, Nakazato H, Kosaki G. Primary structure of human carcinoembryonic antigen (CEA) deduced from cDNA sequences. Biochem Biophys Res Commun. 1987;42:511–511. [Abstract] [Google Scholar]
24. Primus FJ, Kelley EA, Hansen HJ, Goldenberg DM. “Sandwich”-type immunoassay of carcinoembryonic antigen in patients receiving murine antibodies for diagnosis and therapy. Clin Chem. 1988;34:261–261. [Abstract] [Google Scholar]
25. Robbins PF, Kantor JA, Salgaller M, Horan Hand P, Fernsten PD, Schlom J. Transduction and expression of the human carcinoembryonic antigen (CEA) gene in a murine colon carcinoma cell line. Cancer Res. 1991;51:3657–3657. [Abstract] [Google Scholar]
26. Rose TM, Plowman GD, Teplow DB, Dreyer WJ, Hellstrom KE, Brown JP. Primary structure of human melanoma-associated antigen p97 (melanotranferrin) deduced from the mRNA sequence. Proc Natl Acad Sci USA. 1986;83:1261–1261. [Europe PMC free article] [Abstract] [Google Scholar]
27. Schlom J. Basic principle and applications of monoclonal antibodies in the management of carcinomas: the Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res. 1986;46:3225–3225. [Abstract] [Google Scholar]
28. Thor A, Ohuchi N, Szpak CA, Johnston WW, Schlom J. Distribution of oncofetal antigen tumor-associated glycoprotein-72 defined by monoclonal antibody B72.3. Cancer Res. 1986;46:3118–3118. [Abstract] [Google Scholar]
29. Tom BH, Rutzky LH, Jakstys MM, Oyasu R, Kaye CI, Kahan BD. Human colonic adenocarcinoma cells: I. Establishment and description of a new cell line. In Vitro (Rockville) 1976;12:180–180. [Abstract] [Google Scholar]
30. von Kleist S, Burtin P. Antigens cross-reacting with CEA. In: Herberman RB, McIntire KR, editors. Immunodiagnosis of cancer, vol 9. New York: Dekker; 1979. pp. 322–322. [Google Scholar]
31. Wreschner DH, Hareuveni M, Tsarfaty I, Smorodinsky N, Horev J, Zaretsky J, Kotes P, Weiss M, Lathe R, Dion A, Keydar I. Human epithelial tumor antigen cDNA sequences. Differential splicing may generate multiple protein forms. Eur J Biochem. 1990;189:463–463. [Abstract] [Google Scholar]
32. Zimmermann W, Weber B, Ortleib B, Rudert F. Chromosomal localization of the carcinoembryonic antigen gene family and differential expression in various tumors. Cancer Res. 1988;48:2550–2550. [Abstract] [Google Scholar]

Articles from Cancer Immunology, Immunotherapy : CII are provided here courtesy of Springer

Citations & impact 


Impact metrics

Jump to Citations

Citations of article over time

Alternative metrics

Altmetric item for https://www.altmetric.com/details/41218778
Altmetric
Discover the attention surrounding your research
https://www.altmetric.com/details/41218778

Article citations


Go to all (11) article citations