Carcinoembryonic Antigen Transgenic Mouse Models for Immunotherapy and Development of Cancer Vaccines

Malaya Bhattacharya‐Chatterjee1, Asim Saha1, Kenneth A. Foon2, Sunil K. Chatterjee1

1 University of Cincinnati Medical Center, Cincinnati, Ohio, 2 University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania
Publication Name:  Current Protocols in Immunology
Unit Number:  Unit 20.8
DOI:  10.1002/0471142735.im2008s80
Online Posting Date:  February, 2008
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The goal of cancer therapy remains as the long‐term eradication of tumor cells without adverse effects on normal tissue. Conventional approaches utilizing chemotherapy and radiotherapy are limited by both their toxicity and lack of specificity. In recent years, investigators have carried out several studies designed to evaluate whether human tumor‐associated antigens (TAAs) can be exploited as targets for immunotherapy, specifically for human cancer vaccine development. A major limitation in immunotherapy studies of human cancer is the general lack of appropriate preclinical models. Clinical studies can be difficult to implement, particularly when a clear understanding of the potential efficacy, limitation, and safety of an immunotherapeutic strategy is not available from relevant animal investigations. However, mice carrying a transgene for a human tumor self‐antigen may provide a more acceptable experimental model in which knowledge about immunotherapeutic strategies aiming at the TAA of interest can be enhanced prior to initiating clinical trials. Since the different strategies in experimental immunotherapy of cancer have been directed to activate different immune system components, a variety of transgenic mouse models have been generated expressing either TAA, human leukocyte antigen (HLA), oncogene, or immune effector cell molecules. These models may serve as an excellent platform for the identification of novel targets for immunotherapy as well as to evaluate the efficacy of targeted therapies and will lead to the development of clinical trials for cancer patients. In this unit, a brief overview of the generation and study of different vaccine approaches in carcinoembryonic antigen (CEA) transgenic mouse models and the experimental findings in mouse models that spontaneously develop gastrointestinal tumors and express the CEA transgene is provided. Curr. Protoc. Immunol. 80:20.8.1‐20.8.12. © 2008 by John Wiley & Sons, Inc.

Keywords: immunotherapy; cancer; vaccines; transgenic mouse model; carcinoembryonic antigen

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Table of Contents

  • Introduction
  • CEA Transgenic Mice
  • CEA Vaccines
  • CEA‐Based Vaccines in Spontaneous Intestinal Tumor Mouse Model
  • Conclusions
  • Literature Cited
  • Tables
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Literature Cited

Literature Cited
   Abe, H., Kuroki, M., Tachibana, K., Li, T., Awasthi, A., Ueno, A., Matsumoto, H., Imakiire, T., Yamauchi, Y., Yamada, H., Ariyoshi, A., and Kuroki, M. 2002. Targeted sonodynamic therapy of cancer using a photosensitizer conjugated with antibody against carcinoembryonic antigen. Anticancer Res. 22:1575‐1580.
   Agadjanyan, M.G., Kim, J.J., Trivedi, N., Wilson, D.M., Monzavi‐Karbassi, B., Morrison, L.D., Nottingham, L.K., Dentchev, T., Tsai, A., Dang, K., Chalian, A.A., Maldonado, M.A., Williams, W.V., and Weiner, D.B. 1999. CD86 (B7‐2) can function to drive MHC‐restricted antigen‐specific CTL responses in vivo. J. Immunol. 162:3417‐3427.
   Allison, J., Malcolm, L., Chosich, N., and Miller, J.F. 1992. Inflammation but not autoimmunity occurs in transgenic mice expressing constitutive levels of interleukin‐2 in islet beta cells. Eur. J. Immunol. 22:1115‐1121.
   Anand, R., Ma, D., Alizadeh, H., Comerford, S.A., Sambrook, J.F., Gething, M.J., McLean, I.W., and Niederkorn, J.Y. 1994. Characterization of intraocular tumors arising in transgenic mice. Invest. Ophthalmol. Vis. Sci. 35:3533‐3539.
   Banchereau, J., Briere, F., Caux, C., Davoust, J., Lebecque, S., Liu, Y‐J., Pulendran, B., and Palucka, K. 2000. Immunobiology of dendritic cells. Annu. Rev. Immunol. 18:767‐811.
   Baral, R.N., Saha, A., Chatterjee, S.K., Foon, K.A., Krieg, A.M., Weiner, G.J., and Bhattacharya‐Chatterjee, M. 2003. Immunostimulatory CpG oligonucleotides enhance the immune response of anti‐idiotype vaccine that mimics carcinoembryonic antigen. Cancer Immunol. Immunother. 52:317‐327.
   Behr, T.M., Liersch, T., Greiner‐Bechert, L., Griesinger, F., Behe, M., Markus, P.M., Gratz, S., Angerstein, C., Brittinger, G., Becker, H., Goldenberg, D.M., and Becker, W. 2002. Radioimmunotherapy of small‐volume disease of metastatic colorectal cancer. Cancer 94:1373‐1381.
   Berinstein, N.L. 2002. Carcinoembryonic antigen as a target for therapeutic anticancer vaccines: A review. J. Clin. Oncol. 20:2197‐2207.
   Bhattacharya‐Chatterjee, M., Mukherjee, S., Biddle, W., Foon, K.A., and Kohler, H. 1990. Murine monoclonal anti‐idiotype antibody as a potential network antigen for human carcinoembryonic antigen. J. Immunol. 145:2758‐2765.
   Bhattacharya‐Chatterjee, M., Chatterjee, S.K., and Foon, K.A. 2002. Anti‐idiotype antibody vaccine therapy for cancer. Expert. Opin. Biol. Ther. 2:869‐881.
   Brandle, D., Bilsborough, J., Rulicke, T., Uyttenhove, C., Boon, T., and Van der Eynde, B.J. 1998. The shared tumor‐specific antigen encoded by mouse gene P1A is a target not only for cytotoxic T lymphocytes but also for tumor rejection. Eur. J. Immunol. 28:4010‐4019.
   Chakraborty, M., Abrams, S.I., Coleman, C.N., Camphausen, K., Schlom, J., and Hodge, J.W. 2004. External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine‐mediated T‐cell killing. Cancer Res. 64:4328‐4337.
   Chan, C.H. and Stanners, C.P. 2004. Novel mouse model for carcinoembryonic antigen‐based therapy. Mol. Ther. 9:775‐785.
   Clarke, P., Mann, J., Simpson, J.F., Rickard‐Dickson, K., and Primus, F.J. 1998. Mice transgenic for human carcinoembryonic antigen as a model for immunotherapy. Cancer Res. 58:1469‐1477.
   Davila, E., Kennedy, R., and Celis, E. 2003. Generation of antitumor immunity by cytotoxic T lymphocyte epitope peptide vaccination, CpG‐oligodeoxynucleotide adjuvant, and CTLA‐4 blockade. Cancer Res. 63:3281‐3288.
   Donaldson, S.S., Hancock, S.L., and Hoppe, R.T. 1999. The Janeway lecture. Hodgkin's disease—Finding the balance between cure and late effects. Cancer J. Sci. Am. 5:325‐333.
   Durrant, L.G., Buckley, D.J., Robins, R.A., and Spendlove, I. 2000. 105AD7 cancer vaccine stimulates anti‐tumor helper and cytotoxic T‐cell responses in colorectal cancer patients but repeated immunizations are required to maintain these responses. Int. J. Cancer 85:87‐92.
   Eades‐Perner, A.M., van der Putten, H., Hirth, A., Thompson, J., Neumaier, M., von Kleist, S., and Zimmermann, W. 1994. Mice transgenic for the human carcinoembryonic antigen gene maintain its spatiotemporal expression pattern. Cancer Res. 54:4169‐4176.
   Facciabene, A., Aurisicchio, L., Elia, L., Palombo, F., Mennuni, C., Ciliberto, G., and La Monica, N. 2006. DNA and adenoviral vectors encoding carcinoembryonic antigen fused to immunoenhancing sequences augment antigen‐specific immune response and confer tumor protection. Hum. Gene Ther. 17:81‐92.
   Fallarino, F., Fields, P.E., and Gajewski, T.F. 1998. B7‐1 engagement of cytotoxic T lymphocyte antigen 4 inhibits T cell activation in the absence of CD28. J. Exp. Med. 188:205‐210.
   Foon, K.A., John, W.J., Chakraborty, M., Sherratt, A., Garrison, J., Flett, M., and Bhattacharya‐Chatterjee, M. 1997. Clinical and immune responses in advanced colorectal cancer patients treated with anti‐idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen. Clin. Cancer Res. 3:1267‐1276.
   Foon, K.A., John, W.J., Chakraborty, M., Das, R., Teitelbaum, A., Garrison, J., Kashala, O., Chatterjee, S.K., and Bhattacharya‐Chatterjee, M. 1999. Clinical and immune responses in resected colon cancer patients treated with anti‐idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen. J. Clin. Oncol. 17:2889‐2895.
   Garrido, F., Ruiz‐Cabello, F., Cabrera, T., Perez‐Villar, J.J., Lopez‐Botet, M., Duggan‐Keen, M., and Stern, P.L. 1997. Implications for immunosurveillance of altered HLA class I phenotypes in human tumors. Immunol. Today 18:89‐95.
   Gilboa, E. 1999. How tumors escape immune destruction and what we can do about it. Cancer Immunol. Immunother. 48:382‐385.
   Greiner, J.W., Zeytin, H., Anver, M.R., and Schlom, J. 2002. Vaccine‐based therapy directed against carcinoembryonic antigen demonstrates antitumor activity on spontaneous intestinal tumors in the absence of autoimmunity. Cancer Res. 62:6944‐6951.
   Gurunathan, S., Wu, C.Y., Freidag, B.L., and Seder, R.A. 2000. DNA vaccines: A key for inducing long‐term cellular immunity. Curr. Opin. Immunol. 12:442‐447.
   Guy, C.T., Webster, M.A., Schaller, M., Parsons, T.J., Cardiff, R.D., and Muller, W.J. 1992. Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. Proc. Natl. Acad. Sci. U.S.A. 89:10578‐10582.
   Hammarstrom, S., Olsen, A., Teglund, S., and Baranov, V. 1998. The nature and expression of the human CEA family. In Cell Adhesion and Communication Mediated by the CEA Family, Cell Adhesion and Communication Book Series (C.P. Stanners, ed.) pp. 289‐302. Harwood Academic Publishers, Amsterdam.
   Hasegawa, T., Isobe, K., Tsuchiya, Y., Oikawa, S., Nakazato, H., Ikezawa, H., Nakashima, I., and Shimokata, K. 1991. Establishment and characterization of human carcinoembryonic antigen transgenic mice. Br. J. Cancer 64:710‐714.
   Heijnen, I.A. and Van de Winkel, J.G. 1995. A human Fc gamma RI/CD64 transgenic model for in vivo analysis of (bispecific) antibody therapeutics. J. Hematother. 4:351‐356.
   Herlyn, D. and Birebent, B. 1999. Advances in cancer vaccine development. Ann. Med. 31:66‐78.
   Hodge, J.W., Grosenbach, D.W., Aarts, W.M., Poole, D.J., and Schlom, J. 2003a. Vaccine therapy of established tumors in the absence of autoimmunity. Clin. Cancer Res. 9:1837‐1849.
   Hodge, J.W., Poole, D.J., Aarts, W.M., Gomez Yafal, A., Gritz, L., and Schlom, J. 2003b. Modified vaccinia virus ankara recombinants are as potent as vaccinia recombinants in diversified prime and boost vaccine regimens to elicit therapeutic antitumor responses. Cancer Res. 63:7942‐7949.
   Horig, H., Medina, F.A., Conkright, W.A., and Kaufman, H.L. 2000. Strategies for cancer therapy using carcinoembryonic antigen vaccines. Expert Rev. Mol. Med. 2000:1‐24.
   Huang, Y., Fayad, R., Smock, A., Ullrich, A.M., and Qiao, L. 2005. Induction of mucosal and systemic immune responses against human carcinoembryonic antigen by an oral vaccine. Cancer Res. 65:6990‐6999.
   Jerne, N.K. 1974. Towards a network theory of the immune system. Ann. Immunol. (Paris) 125C:373‐389.
   Johnson, L., Mercer, K., Greenbaum, D., Bronson, R.T., Crowley, D., Tuveson, D.A., and Jacks, T. 2001. Somatic activation of the K‐ras oncogene causes early onset lung cancer in mice. Nature 410:1111‐1116.
   Kalams, S.A. and Walker, B.D. 1998. The critical need for CD4 help in maintaining effective cytotoxic T lymphocyte responses. J. Exp. Med. 188:2199‐2204.
   Kawashima, I., Hudson, S.J., Tsai, V., Southwood, S., Takesako, K., Appella, E., Sette, A., and Celis, E. 1998. The multi‐epitope approach for immunotherapy for cancer: Identification of several CTL epitopes from various tumor‐associated antigens expressed on solid epithelial tumors. Hum. Immunol. 59:1‐14.
   Koga, H., Kanda, H., Nakashima, M., Watanabe, Y., Endo, K., and Watanabe, T. 1990. Mouse‐human chimeric monoclonal antibody to carcinoembryonic antigen (CEA): In vitro and in vivo activities. Hybridoma 9:43‐56.
   Krieg, A.M. 2002. CpG motifs in bacterial DNA and their immune effects. Annu. Rev. Immunol. 20:709‐760.
   Kudo‐Saito, C., Schlom, J., and Hodge, J.W. 2005. Induction of an antigen cascade by diversified subcutaneous/intratumoral vaccination is associated with antitumor responses. Clin. Cancer Res. 11:2416‐2426.
   Luo, Y., O'Hagan, D., Zhou, H., Singh, M., Ulmer, J., Reisfeld, R.A., Primus, F.J., and Xiang, R. 2003. Plasmid DNA encoding carcinoembryonic antigen (CEA) adsorbed onto cationic microparticles induces protective immunity against colon cancer in CEA‐transgenic mice. Vaccine 21:1938‐1947.
   Lustgarten, J., Theobald, M., Labadie, C., LaFace, D., Peterson, P., Disis, M.L., Cheever, M.A., and Sherman, L.A. 1997. Identification of Her‐2/Neu CTL epitopes using double transgenic mice expressing HLA‐A2.1 and human CD8. Hum. Immunol. 52:109‐118.
   Manning, T.C., Rund, L.A., Gruber, M.M., Fallarino, F., Gajewski, T.F., and Kranz, D.M. 1997. Antigen recognition and allogeneic tumor rejection in CD8+ TCR transgenic/RAG(−/−) mice. J. Immunol. 159:4665‐4675.
   McCarty, T.M., Yu, Z., Liu, X., Diamond, D.J., and Ellenhorn, J.D. 1998. An HLA‐restricted, p53 specific immune response from HLA transgenic p53 knockout mice. Ann. Surg. Oncol. 5:93‐99.
   Melief, C.J., Toes, R.E., Medema, J.P., van der Burg, S.H., Ossendorp, F., and Offringa, R. 2000. Strategies for immunotherapy of cancer. Adv. Immunol. 75:235‐282.
   Mizobata, S., Tompkins, K., Simpson, J.F., Shyr, Y., and Primus, F.J. 2000. Induction of cytotoxic T cells and their antitumor activity in mice transgenic for carcinoembryonic antigen. Cancer Immunol. Immunother. 49:285‐295.
   Morris, M.J. and Bosl, G.J. 1999. High‐dose chemotherapy as primary treatment for poor‐risk germ‐cell tumors: The Memorial Sloan‐Kettering experience (1988‐1999). Int. J. Cancer 83:834‐838.
   Moser, A.R., Pitot, H.C., and Dove, W.F. 1990. A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. Science 247:322‐324.
   Mukherjee, P., Ginardi, A.R., Madsen, C.S., Sterner, C.J., Adriance, M.C., Tevethia, M.J., and Gendler, S.J. 2000. Mice with spontaneous pancreatic cancer naturally develop MUC‐1‐specific CTLs that eradicate tumors when adoptively transferred. J. Immunol. 165:3451‐3460.
   Ojima, T., Iwahashi, M., Nakamura, M., Matsuda, K., Nakamori, M., Ueda, K., Naka, T., Ishida, K., Primus, F.J., and Yamaue, H. 2006. Successful cancer vaccine therapy for carcinoembryonic antigen (CEA)‐expressing colon cancer using genetically modified dendritic cells that express CEA and T helper‐type 1 cytokines in CEA transgenic mice. Int. J. Cancer 120:585‐593.
   Palmiter, R.D., Brinster, R.L., Hammer, R.E., Trumbauer, M.E., Rosenfeld, M.G., Birnberg, N.C., and Evans, R.M. 1982. Dramatic growth of mice that develop from eggs microinjected with metallothionein‐growth hormone fusion genes. Nature 300:611‐615.
   Pardoll, D.M. and Topalian, S.L. 1998. The role of CD4+ T cell responses in antitumor immunity. Curr. Opin. Immunol. 10:588‐594.
   Penichet, M.L. and Morrison, S.L. 2001. Antibody‐cytokine fusion proteins for the therapy of cancer. J. Immunol. Methods 248:91‐101.
   Pervin, S., Chakraborty, M., Bhattacharya‐Chatterjee, M., Zeytin, H., Foon, K.A., and Chatterjee, S.K. 1997. Induction of antitumor immunity by an anti‐idiotype antibody mimicking carcinoembryonic antigen. Cancer Res. 57:728‐734.
   Piechocki, M.P., Ho, Y.S., Pilon, S., and Wei, W.Z. 2003. Human ErbB‐2 (Her‐2) transgenic mice: A model system for testing Her‐2 based vaccines. J. Immunol. 171:5787‐5794.
   Primus, F.J., Clark, C.A., and Goldenburg, D.M. 1981. Immunoperoxidase localization of carcinoembryonic antigen in normal human intestinal mucosa. J. Natl. Cancer Inst. 67:1031‐1039.
   Reinartz, S., Hombach, A., Kohler, S., Schlebusch, H., Wallwiener, D., Abken, H., and Wagner, U. 2003. Interleukin‐6 fused to an anti‐idiotype antibody in a vaccine increases the specific humoral immune response against CA125+ (MUC‐16) ovarian cancer. Cancer Res. 63:3234‐3240.
   Riethmuller, G., Holz, E., Schlimok, G., Schmiegel, W., Raab, R., Hoffken, K., Gruber, R., Funke, I., Pichlmaier, H., Hirche, H., Buggisch, P., Witte, J., and Pichlmayr, R. 1998. Monoclonal antibody therapy for resected Dukes’ C colorectal cancer: Seven‐year outcome of a multicenter randomized trial. J. Clin. Oncol. 16:1788‐1794.
   Rodriguez, F., Zhang, J., and Whitton, J. 1997. DNA immunization: Ubiquitination of a viral protein enhances cytotoxic T‐lymphocyte induction and antiviral protection but abrogates antibody induction. J. Virol. 71:8497‐8503.
   Romieu, R., Lacabanne, V., Kayibanda, M., Antoine, B., Bennoun, M., Chouaib, S., Guillet, J.G., and Viguier, M. 1997. Critical stages of tumor growth regulation in transgenic mice harboring a hepatocellular carcinoma revealed by distinct patterns of tumor necrosis factor‐ alpha and transforming growth factor‐beta mRNA production. Int. Immunol. 9:1405‐1413.
   Rowse, G.J., Tempero, R.M., VanLith, M.L., Hollingsworth, M.A., and Gendler, S.J. 1998. Tolerance and immunity to MUC1 in a human MUC1 transgenic murine model. Cancer Res. 58:315‐321.
   Saha, A., Chatterjee, S.K., Foon, K.A., Primus, F.J., and Bhattacharya‐Chatterjee, M. 2003. Murine dendritic cells pulsed with an anti‐idiotype antibody induce antigen‐specific protective antitumor immunity. Cancer Res. 63:2844‐2854.
   Saha, A., Chatterjee, S.K., Foon, K.A., Primus, F.J., Sreedharan, S., Mohanty, K., and Bhattacharya‐Chatterjee, M. 2004. Dendritic cells pulsed with an anti‐idiotype antibody mimicking carcinoembryonic antigen (CEA) can reverse immunological tolerance to CEA and induce antitumor immunity in CEA transgenic mice. Cancer Res. 64:4995‐5003.
   Saha, A., Baral, R.N., Chatterjee, S.K., Mohanty, K., Pal, S., Foon, K.A., Primus, F.J., Krieg, A.M., Weiner, G.J., and Bhattacharya‐Chatterjee, M. 2006a. CpG oligonucleotides enhance the tumor antigen‐specific immune response of an anti‐idiotype antibody‐based vaccine strategy in CEA transgenic mice. Cancer Immunol. Immunother. 55:515‐527.
   Saha, A., Chatterjee, S.K., Foon, K.A., and Bhattacharya‐Chatterjee, M. 2006b. Anti‐idiotype antibody induced cellular immunity in mice transgenic for human carcinoembryonic antigen. Immunology 118:483‐496.
   Saha, A., Chatterjee, S.K., Foon, K.A., Celis, E., and Bhattacharya‐Chatterjee, M. 2007. Therapy of established tumors in a novel murine model transgenic for human carcinoembryonic antigen and HLA‐A2 with a combination of anti‐idiotype vaccine and CTL peptides of carcinoembryonic antigen. Cancer Res. 67:2881‐2892.
   Sandler, A.D., Chihara, H., Kobayashi, G., Zhu, X., Miller, M.A., Scott, D.L., and Krieg, A.M. 2003. CpG oligonucleotides enhance the tumor antigen‐specific immune response of a granulocyte macrophage colony‐stimulating factor‐based vaccine strategy in neuroblastoma. Cancer Res. 63:394‐399.
   Schlesinger, S. and Dubensky, T.W. 1999. Alphavirus vectors for gene expression and vaccines. Curr. Opin. Biotechnol. 10:434‐439.
   Schwegler, C., Dorn‐Beineke, A., Nittka, S., Stocking, C., and Neumaier, M. 2005. Monoclonal anti‐idiotype antibody 6G6.C4 fused to GM‐CSF is capable of breaking tolerance to carcinoembryonic antigen (CEA) in CEA‐transgenic mice. Cancer Res. 65:1925‐1933.
   Sha, W.C., Nelson, C.A., Newberry, R.D., Kranz, D.M., Russell, J.H., and Loh, D.Y. 1988. Selective expression of an antigen receptor on CD8‐bearing T lymphocytes in transgenic mice. Nature 335:271‐274.
   Shively, J.E. and Beatty, J.D. 1985. CEA‐related antigens: Molecular biology and clinical significance. Crit. Rev. Oncol. Hematol. 2:355‐399.
   Somasundaram, R., Zaloudik, J., Jacob, L., Benden, A., Sperlagh, M., Hart, E., Marks, G., Kane, M., Mastrangelo, M., and Herlyn, D. 1995. Induction of antigen‐specific T and B cell immunity in colon carcinoma patients by anti‐idiotypic antibody. J. Immunol. 155:3253‐3261.
   Tao, M.H. and Levy, R. 1993. Idiotype/granulocyte‐macrophage colony‐stimulating factor fusion protein as a vaccine for B‐cell lymphoma. Nature 362:755‐758.
   Thompson, J.A., Grunert, F., and Zimmermann, W. 1991. Carcinoembryonic antigen gene family: Molecular biology and clinical perspective. J. Clin. Lab. Anal. 5:344‐366.
   Thompson, J.A., Eades‐Perner, A‐M., Ditter, M., Muller, W.J., and Zimmermann, W. 1997. Expression of transgenic carcinoembryonic antigen (CEA) in tumor‐prone mice: An animal model for CEA‐directed tumor immunotherapy. Int. J. Cancer 72:197‐202.
   Toes, R.E., Ossendorp, F., Offringa, R., and Melief, C.J. 1999. CD4 T cells and their role in antitumor immune responses. J. Exp. Med. 189:753‐756.
   Tsang, K.Y., Zaremba, S., Nieroda, C.A., Zhu, M.Z., Hamilton, J.M., and Schlom, J. 1995. Generation of human cytotoxic T cells specific for human carcinoembryonic antigen epitopes from patients immunized with recombinant vaccinia‐CEA vaccine. J. Natl. Cancer Inst. 87:982‐990.
   van der Bruggen, P., Traversari, C., Chomez, P., Lurquin, C., De Plaen, E., Van den Eynde, B., Knuth, A., and Boon, T. 1991. A gene encoding an antigen recognized by cytotoxic T lymphocytes on a human melanoma. Science 254:1643‐1647.
   van Ojik, H.H., Bevaart, L., Dahle, C.E., Bakker, A., Jansen, M.J., van Vugt, M.J., van de Winkel, J.G., and Weiner, G.J. 2003. CpG‐A and B oligodeoxynucleotides enhance the efficacy of antibody therapy by activating different effector cell populations. Cancer Res. 63:5595‐5600.
   Vitiello, A., Marchesini, D., Furze, J., Sherman, L.A., and Chesnut, R.W. 1991. Analysis of the HLA‐restricted influenza‐specific cytotoxic T lymphocyte response in transgenic mice carrying a chimeric human‐mouse class I major histocompatibility complex. J. Exp. Med. 173:1007‐1015.
   Wei, C., Willis, R.A., Tilton, B.R., Looney, R.J., Lord, E.M., Barth, R.K., and Frelinger, J.G. 1997. Tissue‐specific expression of the human prostate‐specific antigen gene in transgenic mice: Implications for tolerance and immunotherapy. Proc. Natl. Acad. Sci. U.S.A. 94:6369‐6374.
   Wei, C., Callahan, B.P., Turner, M.J., Willis, R.A., Lord, E.M., Barth, R.K., and Frelinger, J.G. 1998. Regulation of human prostate‐specific antigen gene expression in transgenic mice: Evidence for an enhancer between the PSA and human glandular kallikrein‐1 genes. Int. J. Mol. Med. 2:487‐496.
   Wilkinson, R.W., Ross, E.L., Poulsom, R., Ilyas, M., Straub, J., Snary, D., Bodmer, W.F., and Mather, S.J. 2001. Antibody targeting studies in a transgenic murine model of spontaneous colorectal tumors. Proc. Natl. Acad. Sci. U.S.A. 98:10256‐10260.
   Xiang, R., Primus, F.J., Ruehlmann, J.M., Niethammer, A.G., Silletti, S., Lode, H.N., Dolman, C.S., Gillies, S.D., and Reisfeld, R.A. 2001a. A dual‐function DNA vaccine encoding carcinoembryonic antigen and CD40 ligand trimer induces T cell–mediated protective immunity against colon cancer in carcinoembryonic antigen‐transgenic mice. J. Immunol. 167:4560‐4565.
   Xiang, R., Silletti, S., Lode, H.N., Dilman, C.S., Ruehlmann, J.M., Niethammer, A.G., Pertl, U., Gillies, S.D., Primus, F.J., and Reisfeld, R.A. 2001b. Protective immunity against human carcinoembryonic antigen (CEA) induced by an oral DNA vaccine in CEA‐transgenic mice. Clin. Cancer Res. 307:856s‐864s.
   Xu, X., Clarke, P., Szalai, G., Shively, J.E., Williams, L.E., Shyr, Y., Shi, E., and Primus, F.J. 2000. Targeting and therapy of carcinoembryonic antigen‐expressing tumors in transgenic mice with an antibody‐interleukin 2 fusion protein. Cancer Res. 60:4475‐4484.
   Yu, Z., Liu, X., McCarty, T.M., Diamond, D.J., and Ellenhorn, J.D. 1997. The use of transgenic mice to generate high affinity p53 specific cytolytic T cells. J. Surg. Res. 69:337‐343.
   Zeytin, H.E., Patel, A.C., Rogers, C.J., Canter, D., Hursting, S.D., Schlom, J., and Greiner, J.W. 2004. Combination of a poxvirus‐based vaccine with a cyclooxygenase‐2 inhibitor (Celecoxib) elicits antitumor immunity and long‐term survival in CEA.Tg/MIN mice. Cancer Res. 64:3668‐3678.
   Zhou, H., Luo, Y., Mizutani, M., Mizutani, N., Becker, J.C., Primus, F.J., Xiang, R., and Reisfeld, R.A. 2004. A novel transgenic mouse model for immunological evaluation of carcinoembryonic antigen‐based DNA minigene vaccines. J. Clin. Invest. 113:1792‐1798.
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