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Expert Review of Vaccines Volume 12, 2013 - Issue 6
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Review

Cancer vaccines targeting carcinoembryonic antigen: state-of-the-art and future promise

Sofia R Gameiro Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
,
Momodou L Jammeh Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
&
James W Hodge Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA. [email protected]
Pages 617-629 | Published online: 09 Jan 2014

References

  • Benchimol S, Fuks A, Jothy S, Beauchemin N, Shirota K, Stanners CP. Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. Cell 57(2), 327–334 (1989).
  • Thompson JA, Grunert F, Zimmermann W. Carcinoembryonic antigen gene family: molecular biology and clinical perspectives. J. Clin. Lab. Anal. 5(5), 344–366 (1991).
  • Diamandis EP, Bast RC Jr, Gold P, Chu TM, Magnani JL. Reflection on the discovery of carcinoembryonic antigen, prostate-specific antigen, and cancer antigens CA125 and CA19-9. Clin. Chem. 59(1), 22–31 (2013).
  • Guadagni F, Roselli M, Cosimelli M et al. Quantitative analysis of CEA expression in colorectal adenocarcinoma and serum: lack of correlation. Int. J. Cancer 72(6), 949–954 (1997).
  • Robbins PF, Eggensperger D, Qi CF, Schlom J. Definition of the expression of the human carcinoembryonic antigen and non-specific cross-reacting antigen in human breast and lung carcinomas. Int. J. Cancer 53(6), 892–897 (1993).
  • Tendler A, Kaufman HL, Kadish AS. Increased carcinoembryonic antigen expression in cervical intraepithelial neoplasia grade 3 and in cervical squamous cell carcinoma. Hum. Pathol. 31(11), 1357–1362 (2000).
  • Thomas P, Forse RA, Bajenova O. Carcinoembryonic antigen (CEA) and its receptor hnRNP M are mediators of metastasis and the inflammatory response in the liver. Clin. Exp. Metastasis 28(8), 923–932 (2011).
  • Minami S, Furui J, Kanematsu T. Role of carcinoembryonic antigen in the progression of colon cancer cells that express carbohydrate antigen. Cancer Res. 61(6), 2732–2735 (2001).
  • Wang J, Ma Y, Zhu ZH, Situ DR, Hu Y, Rong TH. Expression and prognostic relevance of tumor carcinoembryonic antigen in stage IB non-small cell lung cancer. J. Thorac. Dis. 4(5), 490–496 (2012).
  • Lee JH, Kim SH, Jang HS et al. Preoperative elevation of carcinoembryonic antigen predicts poor tumor response and frequent distant recurrence for patients with rectal cancer who receive preoperative chemoradiotherapy and total mesorectal excision: a multi-institutional analysis in an Asian population. Int. J. Colorectal Dis. 28(4), 511–517 (2013).
  • Grunnet M, Sorensen JB. Carcinoembryonic antigen (CEA) as tumor marker in lung cancer. Lung Cancer 76(2), 138–143 (2012).
  • Kato T, Ishikawa K, Aragaki M et al. Optimal predictive value of preoperative serum carcinoembryonic antigen for surgical outcomes in stage I non-small cell lung cancer: differences according to histology and smoking status. J. Surg. Oncol. 107(6), 619–624 (2013).
  • Chmielewski M, Hahn O, Rappl G et al. T cells that target carcinoembryonic antigen eradicate orthotopic pancreatic carcinomas without inducing autoimmune colitis in mice. Gastroenterology 143(4), 1095–1107.e2 (2012).
  • Brämswig KH, Knittelfelder R, Gruber S et al. Immunization with mimotopes prevents growth of carcinoembryonic antigen positive tumors in BALB/c mice. Clin. Cancer Res. 13(21), 6501–6508 (2007).
  • Chakraborty M, Gelbard A, Carrasquillo JA et al. Use of radiolabeled monoclonal antibody to enhance vaccine-mediated antitumor effects. Cancer Immunol. Immunother. 57(8), 1173–1183 (2008).
  • Bhattacharya-Chatterjee M, Saha A, Foon KA, Chatterjee SK. Carcinoembryonic antigen transgenic mouse models for immunotherapy and development of cancer vaccines. Curr. Protoc. Immunol. Chapter 20, Unit 20.8 (2008).
  • Mori F, Giannetti P, Peruzzi D et al. A therapeutic cancer vaccine targeting carcinoembryonic antigen in intestinal carcinomas. Hum. Gene Ther. 20(2), 125–136 (2009).
  • Höchst B, Schildberg FA, Böttcher J et al. Liver sinusoidal endothelial cells contribute to CD8 T cell tolerance toward circulating carcinoembryonic antigen in mice. Hepatology 56(5), 1924–1933 (2012).
  • Bereta M, Hayhurst A, Gajda M et al. Improving tumor targeting and therapeutic potential of Salmonella VNP20009 by displaying cell surface CEA-specific antibodies. Vaccine 25(21), 4183–4192 (2007).
  • Hong X, Dong T, Hu J et al. Synergistical toll-like receptors activated dendritic cells induce antitumor effects against carcinoembryonic antigen-expressing colon cancer. Int. J. Colorectal. Dis. 28(1), 25–33 (2012).
  • Park MY, Kim HS, Woo SJ et al. Efficient antitumor immunity in a murine colorectal cancer model induced by CEA RNA-electroporated B cells. Eur. J. Immunol. 38(8), 2106–2117 (2008).
  • Vasir B, Zarwan C, Ahmad R et al. Induction of antitumor immunity ex vivo using dendritic cells transduced with fowl pox vector expressing MUC1, CEA, and a triad of costimulatory molecules (rF-PANVAC). J. Immunother. 35(7), 555–569 (2012).
  • Bae MY, Cho NH, Seong SY. Protective anti-tumour immune responses by murine dendritic cells pulsed with recombinant Tat-carcinoembryonic antigen derived from Escherichia coli. Clin. Exp. Immunol. 157(1), 128–138 (2009).
  • Kim SG, Park MY, Kim CH et al. Modification of CEA with both CRT and TAT PTD induces potent anti-tumor immune responses in RNA-pulsed DC vaccination. Vaccine 26(50), 6433–6440 (2008).
  • Park JS, Kim HS, Park HM, Kim CH, Kim TG. Efficient induction of anti-tumor immunity by a TAT-CEA fusion protein vaccine with poly(I:C) in a murine colorectal tumor model. Vaccine 29(47), 8642–8648 (2011).
  • Kim HS, Kim CH, Park MY et al. Efficient co-transduction of adenoviral vectors encoding carcinoembryonic antigen and survivin into dendritic cells by the CAR-TAT adaptor molecule enhance anti-tumor immunity in a murine colorectal cancer model. Immunol. Lett. 131(1), 73–80 (2010).
  • Li D, Hua S, Fan Y et al. DNA vaccine expressing repeated carcinoembryonic antigen (CEA)(625–667) induces strong immunity in mice. Immunol. Lett. 135(1–2), 124–128 (2011).
  • Bråve A, Hallengärd D, Gudmundsdotter L et al. Late administration of plasmid DNA by intradermal electroporation efficiently boosts DNA-primed T and B cell responses to carcinoembryonic antigen. Vaccine 27(28), 3692–3696 (2009).
  • Lee YJ, Han SR, Kim NY, Lee SH, Jeong JS, Lee SW. An RNA aptamer that binds carcinoembryonic antigen inhibits hepatic metastasis of colon cancer cells in mice. Gastroenterology 143(1), 155–165.e8 (2012).
  • Sarkar K, Goswami S, Roy S et al. Neem leaf glycoprotein enhances carcinoembryonic antigen presentation of dendritic cells to T and B cells for induction of anti-tumor immunity by allowing generation of immune effector/memory response. Int. Immunopharmacol. 10(8), 865–874 (2010).
  • Ardiani A, Higgins JP, Hodge JW. Vaccines based on whole recombinant Saccharomyces cerevisiae cells. FEMS Yeast Res. 10(8), 1060–1069 (2010).
  • Bernstein MB, Chakraborty M, Wansley EK et al. Recombinant Saccharomyces cerevisiae (yeast-CEA) as a potent activator of murine dendritic cells. Vaccine 26(4), 509–521 (2008).
  • Wansley EK, Chakraborty M, Hance KW et al. Vaccination with a recombinant Saccharomyces cerevisiae expressing a tumor antigen breaks immune tolerance and elicits therapeutic antitumor responses. Clin. Cancer Res. 14(13), 4316–4325 (2008).
  • Remondo C, Cereda V, Mostböck S et al. Human dendritic cell maturation and activation by a heat-killed recombinant yeast (Saccharomyces cerevisiae) vector encoding carcinoembryonic antigen. Vaccine 27(7), 987–994 (2009).
  • Cereda V, Vergati M, Huen NY et al. Maturation of human dendritic cells with Saccharomyces cerevisiae (yeast) reduces the number and function of regulatory T cells and enhances the ratio of antigen-specific effectors to regulatory T cells. Vaccine 29(31), 4992–4999 (2011).
  • Eades-Perner AM, van der Putten H, Hirth A et al. Mice transgenic for the human carcinoembryonic antigen gene maintain its spatiotemporal expression pattern. Cancer Res. 54(15), 4169–4176 (1994).
  • Gameiro SR, Caballero JA, Higgins JP, Apelian D, Hodge JW. Exploitation of differential homeostatic proliferation of T-cell subsets following chemotherapy to enhance the efficacy of vaccine-mediated antitumor responses. Cancer Immunol. Immunother. 60(9), 1227–1242 (2011).
  • Ilantzis C, Jothy S, Alpert LC, Draber P, Stanners CP. Cell-surface levels of human carcinoembryonic antigen are inversely correlated with colonocyte differentiation in colon carcinogenesis. Lab. Invest. 76(5), 703–716 (1997).
  • Kim-Schulze S, Kim HS, Wainstein A et al. Intrarectal vaccination with recombinant vaccinia virus expressing carcinoembronic antigen induces mucosal and systemic immunity and prevents progression of colorectal cancer. J. Immunol. 181(11), 8112–8119 (2008).
  • Farsaci B, Kwalis A, Hodge JW. Design, development and translation of poxvirus-based vaccines for cancer. In: Cancer Vaccines: From Research to Clinical Practice. Bot A, Obrocea M, Marincola F (Eds). Informa Healthcare Books, London, UK, 55–77 (2011).
  • Yang S, Schlom J. Antigen-presenting cells containing multiple costimulatory molecules promote activation and expansion of human antigen-specific memory CD8+ T cells. Cancer Immunol. Immunother. 58(4), 503–515 (2009).
  • Cawood R, Hills T, Wong SL et al. Recombinant viral vaccines for cancer. Trends Mol. Med. 18(9), 564–574 (2012).
  • Yang S, Hodge JW, Grosenbach DW, Schlom J. Vaccines with enhanced costimulation maintain high avidity memory CTL. J. Immunol. 175(6), 3715–3723 (2005).
  • Yang S, Tsang KY, Schlom J. Induction of higher-avidity human CTLs by vector-mediated enhanced costimulation of antigen-presenting cells. Clin. Cancer Res. 11(15), 5603–5615 (2005).
  • Hodge JW, Higgins J, Schlom J. Harnessing the unique local immunostimulatory properties of modified vaccinia Ankara (MVA) virus to generate superior tumor-specific immune responses and antitumor activity in a diversified prime and boost vaccine regimen. Vaccine 27(33), 4475–4482 (2009).
  • de Gruijl TD, van de Ven R. Chapter six – adenovirus-based immunotherapy of cancer: promises to keep. Adv. Cancer Res. 115, 147–220 (2012).
  • Facciabene A, Aurisicchio L, Elia L et al. Vectors encoding carcinoembryonic antigen fused to the B subunit of heat-labile enterotoxin elicit antigen-specific immune responses and antitumor effects. Vaccine 26(1), 47–58 (2007).
  • Xu C, Sun Y, Wang Y et al. CEA promoter-regulated oncolytic adenovirus-mediated Hsp70 expression in immune gene therapy for pancreatic cancer. Cancer Lett. 319(2), 154–163 (2012).
  • Peruzzi D, Dharmapuri S, Cirillo A et al. A novel chimpanzee serotype-based adenoviral vector as delivery tool for cancer vaccines. Vaccine 27(9), 1293–1300 (2009).
  • Hodge JW, Ardiani A, Farsaci B, Kwilas AR, Gameiro SR. The tipping point for combination therapy: cancer vaccines with radiation, chemotherapy, or targeted small molecule inhibitors. Semin. Oncol. 39(3), 323–339 (2012).
  • Garnett CT, Schlom J, Hodge JW. Combination of docetaxel and recombinant vaccine enhances T-cell responses and antitumor activity: effects of docetaxel on immune enhancement. Clin. Cancer Res. 14(11), 3536–3544 (2008).
  • Chakraborty M, Schlom J, Hodge JW. The combined activation of positive costimulatory signals with modulation of a negative costimulatory signal for the enhancement of vaccine-mediated T-cell responses. Cancer Immunol. Immunother. 56(9), 1471–1484 (2007).
  • Hance KW, Rogers CJ, Zaharoff DA, Canter D, Schlom J, Greiner JW. The antitumor and immunoadjuvant effects of IFN-α in combination with recombinant poxvirus vaccines. Clin. Cancer Res. 15(7), 2387–2396 (2009).
  • Farsaci B, Sabzevari H, Higgins JP et al. Effect of a small molecule BCL-2 inhibitor on immune function and use with a recombinant vaccine. Int. J. Cancer 127(7), 1603–1613 (2010).
  • Farsaci B, Higgins JP, Hodge JW. Consequence of dose scheduling of sunitinib on host immune response elements and vaccine combination therapy. Int. J. Cancer 130(8), 1948–1959 (2012).
  • Hodge JW, Sharp HJ, Gameiro SR. Abscopal regression of antigen disparate tumors by antigen cascade after systemic tumor vaccination in combination with local tumor radiation. Cancer Biother. Radiopharm. 27(1), 12–22 (2012).
  • Boehm AL, Higgins J, Franzusoff A, Schlom J, Hodge JW. Concurrent vaccination with two distinct vaccine platforms targeting the same antigen generates phenotypically and functionally distinct T-cell populations. Cancer Immunol. Immunother. 59(3), 397–408 (2010).
  • Saha A, Chatterjee SK. Combination of CTL-associated antigen-4 blockade and depletion of CD25 regulatory T cells enhance tumour immunity of dendritic cell-based vaccine in a mouse model of colon cancer. Scand. J. Immunol. 71(2), 70–82 (2010).
  • Kim HS, Park HM, Park JS et al. Dendritic cell vaccine in addition to FOLFIRI regimen improve antitumor effects through the inhibition of immunosuppressive cells in murine colorectal cancer model. Vaccine 28(49), 7787–7796 (2010).
  • Sakakibara M, Kanto T, Hayakawa M et al. Comprehensive immunological analyses of colorectal cancer patients in the Phase I/II study of quickly matured dendritic cell vaccine pulsed with carcinoembryonic antigen peptide. Cancer Immunol. Immunother. 60(11), 1565–1575 (2011).
  • Lesterhuis WJ, De Vries IJ, Schreibelt G et al. Immunogenicity of dendritic cells pulsed with CEA peptide or transfected with CEA mRNA for vaccination of colorectal cancer patients. Anticancer Res. 30(12), 5091–5097 (2010).
  • Kavanagh B, Ko A, Venook A et al. Vaccination of metastatic colorectal cancer patients with matured dendritic cells loaded with multiple major histocompatibility complex class I peptides. J. Immunother. 30(7), 762–772 (2007).
  • Rittig SM, Haentschel M, Weimer KJ et al. Intradermal vaccinations with RNA coding for TAA generate CD8+ and CD4+ immune responses and induce clinical benefit in vaccinated patients. Mol. Ther. 19(5), 990–999 (2011).
  • Morse MA, Hobeika AC, Osada T et al. An alphavirus vector overcomes the presence of neutralizing antibodies and elevated numbers of Tregs to induce immune responses in humans with advanced cancer. J. Clin. Invest. 120(9), 3234–3241 (2010).
  • Zaremba S, Barzaga E, Zhu M, Soares N, Tsang KY, Schlom J. Identification of an enhancer agonist cytotoxic T lymphocyte peptide from human carcinoembryonic antigen. Cancer Res. 57(20), 4570–4577 (1997).
  • Galanis E, Hartmann LC, Cliby WA et al. Phase I trial of intraperitoneal administration of an oncolytic measles virus strain engineered to express carcinoembryonic antigen for recurrent ovarian cancer. Cancer Res. 70(3), 875–882 (2010).
  • Madan RA, Bilusic M, Heery C, Schlom J, Gulley JL. Clinical evaluation of TRICOM vector therapeutic cancer vaccines. Semin. Oncol. 39(3), 296–304 (2012).
  • Tsang KY, Palena C, Gulley J, Arlen P, Schlom J. A human cytotoxic T-lymphocyte epitope and its agonist epitope from the nonvariable number of tandem repeat sequence of MUC-1. Clin. Cancer Res. 10(6), 2139–2149 (2004).
  • Madan RA, Arlen PM, Gulley JL. PANVAC-VF: poxviral-based vaccine therapy targeting CEA and MUC1 in carcinoma. Expert Opin. Biol. Ther. 7(4), 543–554 (2007).
  • Gulley JL, Arlen PM, Tsang KY et al. Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM poxviral-based vaccines in patients with metastatic carcinoma. Clin. Cancer Res. 14(10), 3060–3069 (2008).
  • Mohebtash M, Tsang KY, Madan RA et al. A pilot study of MUC-1/CEA/TRICOM poxviral-based vaccine in patients with metastatic breast and ovarian cancer. Clin. Cancer Res. 17(22), 7164–7173 (2011).
  • Pelzer U, Schwaner I, Stieler J et al. Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a Phase III-study from the German CONKO-study group. Eur. J. Cancer 47(11), 1676–1681 (2011).
  • Lou E, Marshall J, Aklilu M, Cole D, Chang D, Morse M. A Phase II study of active immunotherapy with PANVAC or autologous, cultured dendritic cells infected with PANVAC after complete resection of hepatic metastases of colorectal carcinoma. Clin. Colorectal Cancer 5(5), 368–371 (2006).
  • Bilusic M, Gulley JL, Hodge JW et al. A Phase I trial of a recombinant CEA yeast-based vaccine targeting CEA-expressing cancers. J. Clin. Oncol. 30(Suppl. 4), Abstract 458 (2012).
  • Heery CR, Ibrahim NK, Mohebtash M et al. A Phase 2 randomized trial of docetaxel alone or in combination with therapeutic cancer vaccine, CEA-, MUC-1-TRICOM. Cancer Res. 72(24 Suppl. 3), Abstract nr P5-16-06 (2012).
  • Schlom J. Therapeutic cancer vaccines: current status and moving forward. J. Natl. Cancer Inst. 104(8), 599–613 (2012).
  • Kaufman HL, Lenz HJ, Marshall J et al. Combination chemotherapy and ALVAC-CEA/B7.1 vaccine in patients with metastatic colorectal cancer. Clin. Cancer Res. 14(15), 4843–4849 (2008).
  • Zhong R, Teng J, Han B, Zhong H. Dendritic cells combining with cytokine-induced killer cells synergize chemotherapy in patients with late-stage non-small cell lung cancer. Cancer Immunol. Immunother. 60(10), 1497–1502 (2011).
  • Morse MA, Hobeika AC, Osada T et al. Depletion of human regulatory T cells specifically enhances antigen-specific immune responses to cancer vaccines. Blood 112(3), 610–618 (2008).
  • Staff C, Mozaffari F, Haller BK, Wahren B, Liljefors M. A Phase I safety study of plasmid DNA immunization targeting carcinoembryonic antigen in colorectal cancer patients. Vaccine 29(39), 6817–6822 (2011).
  • Kwilas AR, Donahue RN, Bernstein MB, Hodge JW. In the field: exploiting the untapped potential of immunogenic modulation by radiation in combination with immunotherapy for the treatment of cancer. Front. Oncol. 2, 104 (2012).
  • Gulley JL, Madan RA, Tsang KY et al. A pilot safety trial investigating a vector-based vaccine targeting carcinoembryonic antigen in combination with radiotherapy in patients with gastrointestinal malignancies metastatic to the liver. Expert Opin. Biol. Ther. 11(11), 1409–1418 (2011).
  • Stein WD, Gulley JL, Schlom J et al. Tumor regression and growth rates determined in five intramural NCI prostate cancer trials: the growth rate constant as an indicator of therapeutic efficacy. Clin. Cancer Res. 17(4), 907–917 (2011).
  • Zeytin HE, Patel AC, Rogers CJ et al. 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(10), 3668–3678 (2004).
  • Lesterhuis WJ, de Vries IJ, Aarntzen EA et al. A pilot study on the immunogenicity of dendritic cell vaccination during adjuvant oxaliplatin/capecitabine chemotherapy in colon cancer patients. Br. J. Cancer 103(9), 1415–1421 (2010).

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