IMMUNE NETWORK

The Korean Association of Immunobiologists (대한면역학회)
권호 표지
DOI QR코드

DOI QR Code

Cell-based Immunotherapy for Colorectal Cancer with Cytokine-induced Killer Cells

  • Ji Sung Kim (College of Pharmacy, Chungbuk National University) ;
  • Yong Guk Kim (College of Pharmacy, Chungbuk National University) ;
  • Eun Jae Park (College of Pharmacy, Chungbuk National University) ;
  • Boyeong Kim (College of Pharmacy, Chungbuk National University) ;
  • Hong Kyung Lee (College of Pharmacy, Chungbuk National University) ;
  • Jin Tae Hong (College of Pharmacy, Chungbuk National University) ;
  • Youngsoo Kim (College of Pharmacy, Chungbuk National University) ;
  • Sang-Bae Han (College of Pharmacy, Chungbuk National University)
  • Received : 2015.12.31
  • Accepted : 2016.02.16
  • Published : 2016.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Colorectal cancer is the third leading cancer worldwide. Although incidence and mortality of colorectal cancer are gradually decreasing in the US, patients with metastatic colorectal cancer have poor prognosis with an estimated 5-year survival rate of less than 10%. Over the past decade, advances in combination chemotherapy regimens for colorectal cancer have led to significant improvement in progression-free and overall survival. However, patients with metastatic disease gain little clinical benefit from conventional therapy, which is associated with grade 3~4 toxicity with negative effects on quality of life. In previous clinical studies, cell-based immunotherapy using dendritic cell vaccines and sentinel lymph node T cell therapy showed promising therapeutic results for metastatic colorectal cancer. In our preclinical and previous clinical studies, cytokine-induced killer (CIK) cells treatment for colorectal cancer showed favorable responses without toxicities. Here, we review current treatment options for colorectal cancer and summarize available clinical studies utilizing cell-based immunotherapy. Based on these studies, we recommend the use CIK cell therapy as a promising therapeutic strategy for patients with metastatic colorectal cancer.

Keywords

Acknowledgement

This work was supported by the research grant of the Chungbuk National University in 2014.

References

  1. Ferlay, J., I. Soerjomataram, R. Dikshit, S. Eser, C. Mathers, M. Rebelo, D. M. Parkin, D. Forman, and F. Bray. 2015. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 136: E359-386.  https://doi.org/10.1002/ijc.29210
  2. Siegel, R. L., K. D. Miller, and A. Jemal. 2015. Cancer statistics, 2015. CA Cancer J. Clin. 65: 5-29.  https://doi.org/10.3322/caac.21254
  3. Center, M. M., A. Jemal, and E. Ward. 2009. International trends in colorectal cancer incidence rates. Cancer Epidemiol. Biomarkers Prev. 18: 1688-1694.  https://doi.org/10.1158/1055-9965.EPI-09-0090
  4. Kindler, H. L., and K. L. Shulman. 2001. Metastatic colorectal cancer. Curr. Treat. Options Oncol. 2: 459-471.  https://doi.org/10.1007/s11864-001-0068-7
  5. Sanoff, H. K., D. J. Sargent, M. E. Campbell, R. F. Morton, C. S. Fuchs, R. K. Ramanathan, S. K. Williamson, B. P. Findlay, H. C. Pitot, and R. M. Goldberg. 2008. Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer: N9741. J. Clin. Oncol. 26: 5721-5727.  https://doi.org/10.1200/JCO.2008.17.7147
  6. Cho, E., S. A. Smith-Warner, J. Ritz, P. A. van den Brandt, G. A. Colditz, A. R. Folsom, J. L. Freudenheim, E. Giovannucci, R. A. Goldbohm, S. Graham, L. Holmberg, D. H. Kim, N. Malila, A. B. Miller, P. Pietinen, T. E. Rohan, T. A. Sellers, F. E. Speizer, W. C. Willett, A. Wolk, and D. J. Hunter. 2004. Alcohol intake and colorectal cancer: a pooled analysis of 8 cohort studies. Ann. Intern. Med. 140: 603-613.  https://doi.org/10.7326/0003-4819-140-8-200404200-00007
  7. Liang, P. S., T. Y. Chen, and E. Giovannucci. 2009. Cigarette smoking and colorectal cancer incidence and mortality: systematic review and meta-analysis. Int. J. Cancer 124: 2406-2415.  https://doi.org/10.1002/ijc.24191
  8. Chan, D. S., R. Lau, D. Aune, R. Vieira, D. C. Greenwood, E. Kampman, and T. Norat. 2011. Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies. PLoS One 6: e20456. 
  9. Ma, Y., Y. Yang, F. Wang, P. Zhang, C. Shi, Y. Zou, and H. Qin. 2013. Obesity and risk of colorectal cancer: a systematic review of prospective studies. PLoS One 8: e53916. 
  10. Jiang, Y., Q. Ben, H. Shen, W. Lu, Y. Zhang, and J. Zhu. 2011. Diabetes mellitus and incidence and mortality of colorectal cancer: a systematic review and meta-analysis of cohort studies. Eur. J. Epidemiol. 26: 863-876.  https://doi.org/10.1007/s10654-011-9617-y
  11. Jess, T., C. Rungoe, and L. Peyrin-Biroulet. 2012. Risk of colorectal cancer in patients with ulcerative colitis: a meta-analysis of population-based cohort studies. Clin. Gastroenterol. Hepatol. 10: 639-645.  https://doi.org/10.1016/j.cgh.2012.01.010
  12. Taylor, D. P., R. W. Burt, M. S. Williams, P. J. Haug, and L. A. Cannon-Albright. 2010. Population-based family history-specific risks for colorectal cancer: a constellation approach. Gastroenterology 138: 877-885.  https://doi.org/10.1053/j.gastro.2009.11.044
  13. Haggar, F. A., and R. P. Boushey. 2009. Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin. Colon Rectal Surg. 22: 191-197.  https://doi.org/10.1055/s-0029-1242458
  14. von Roon, A. C., G. Reese, J. Teare, V. Constantinides, A. W. Darzi, and P. P. Tekkis. 2007. The risk of cancer in patients with Crohn's disease. Dis. Colon Rectum 50: 839-855.  https://doi.org/10.1007/s10350-006-0848-z
  15. Lakatos, P. L., and L. Lakatos. 2008. Risk for colorectal cancer in ulcerative colitis: changes, causes and management strategies. World J. Gastroenterol. 14: 3937-3947.  https://doi.org/10.3748/wjg.14.3937
  16. Hampel, H., W. L. Frankel, E. Martin, M. Arnold, K. Khanduja, P. Kuebler, M. Clendenning, K. Sotamaa, T. Prior, J. A. Westman, J. Panescu, D. Fix, J. Lockman, J. LaJeunesse, I. Comeras, and A. de la Chapelle. 2008. Feasibility of screening for Lynch syndrome among patients with colorectal cancer. J. Clin. Oncol. 26: 5783-5788.  https://doi.org/10.1200/JCO.2008.17.5950
  17. Jasperson, K. W., T. M. Tuohy, D. W. Neklason, and R. W. Burt. 2010. Hereditary and familial colon cancer. Gastroenterology 138: 2044-2058.  https://doi.org/10.1053/j.gastro.2010.01.054
  18. Fearon, E. R., and B. Vogelstein. 1990. A genetic model for colorectal tumorigenesis. Cell 61: 759-767.  https://doi.org/10.1016/0092-8674(90)90186-I
  19. Lengauer, C., K. W. Kinzler, and B. Vogelstein. 1998. Genetic instabilities in human cancers. Nature 396: 643-649.  https://doi.org/10.1038/25292
  20. Lothe, R. A., P. Peltomaki, G. I. Meling, L. A. Aaltonen, M. Nystrom-Lahti, L. Pylkkanen, K. Heimdal, T. I. Andersen, P. Moller, T. O. Rognum, S. D. Fossa, T. Haldorsen, F. Langmark, A. Brogger, A. de la Chapelle, and A. Borresen. 1993. Genomic instability in colorectal cancer: relationship to clinicopathological variables and family history. Cancer Res. 53: 5849-5852. 
  21. Grady, W. M., and J. M. Carethers. 2008. Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology 135: 1079-1099.  https://doi.org/10.1053/j.gastro.2008.07.076
  22. Powell, S. M., N. Zilz, Y. Beazer-Barclay, T. M. Bryan, S. R. Hamilton, S. N. Thibodeau, B. Vogelstein, and K. W. Kinzler. 1992. APC mutations occur early during colorectal tumorigenesis. Nature 359: 235-237.  https://doi.org/10.1038/359235a0
  23. Aaltonen, L. A., P. Peltomaki, F. S. Leach, P. Sistonen, L. Pylkkanen, J. P. Mecklin, H. Jarvinen, S. M. Powell, J. Jen, S. R. Hamilton, G. M. Petersen, K. W. Kinzler, B. Vogelstein, and A. de la Chapellet. 1993. Clues to the pathogenesis of familial colorectal cancer. Science 260: 812-816.  https://doi.org/10.1126/science.8484121
  24. Ionov, Y., M. A. Peinado, S. Malkhosyan, D. Shibata, and M. Perucho. 1993. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 363: 558-561.  https://doi.org/10.1038/363558a0
  25. Kane, M. F., M. Loda, G. M. Gaida, J. Lipman, R. Mishra, H. Goldman, J. M. Jessup, and R. Kolodner. 1997. Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res. 57: 808-811. 
  26. Cunningham, D., W. Atkin, H. J. Lenz, H. T. Lynch, B. Minsky, B. Nordlinger, and N. Starling. 2010. Colorectal cancer. Lancet 375: 1030-1047.  https://doi.org/10.1016/S0140-6736(10)60353-4
  27. Shen, L., M. Toyota, Y. Kondo, E. Lin, L. Zhang, Y. Guo, N. S. Hernandez, X. Chen, S. Ahmed, K. Konishi, S. R. Hamilton, and J. P. Issa. 2007. Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer. Proc. Natl. Acad. Sci. U. S. A. 104: 18654-18659.  https://doi.org/10.1073/pnas.0704652104
  28. Pino, M. S., and D. C. Chung. 2010. The chromosomal instability pathway in colon cancer. Gastroenterology 138: 2059-2072.  https://doi.org/10.1053/j.gastro.2009.12.065
  29. Benson, A. B., 3rd, D. Schrag, M. R. Somerfield, A. M. Cohen, A. T. Figueredo, P. J. Flynn, M. K. Krzyzanowska, J. Maroun, P. McAllister, E. Van Cutsem, M. Brouwers, M. Charette, and D. G. Haller. 2004. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J. Clin. Oncol. 22: 3408-3419.  https://doi.org/10.1200/JCO.2004.05.063
  30. Brenner, H., M. Kloor, and C. P. Pox. 2014. Colorectal cancer. Lancet 383: 1490-1502.  https://doi.org/10.1016/S0140-6736(13)61649-9
  31. 1995. Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators. Lancet 345: 939-944.  https://doi.org/10.1016/S0140-6736(95)90696-7
  32. Tournigand, C., T. Andre, E. Achille, G. Lledo, M. Flesh, D. Mery-Mignard, E. Quinaux, C. Couteau, M. Buyse, G. Ganem, B. Landi, P. Colin, C. Louvet, and A. de Gramont. 2004. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J. Clin. Oncol. 22: 229-237.  https://doi.org/10.1200/JCO.2004.05.113
  33. Andrea, C., P. Fausto, B. K. Francesca, C. Mary, G. Mara, L. Veronica, and B. Sandro. 2014. Which strategy after first-line therapy in advanced colorectal cancer? World J. Gastroenterol. 20: 8921-8927. 
  34. Braun, M. S., and M. T. Seymour. 2011. Balancing the efficacy and toxicity of chemotherapy in colorectal cancer. Ther. Adv. Med. Oncol. 3: 43-52.  https://doi.org/10.1177/1758834010388342
  35. Hohla, F., T. Winder, R. Greil, F. G. Rick, N. L. Block, and A. V. Schally. 2014. Targeted therapy in advanced metastatic colorectal cancer: current concepts and perspectives. World J. Gastroenterol. 20: 6102-6112.  https://doi.org/10.3748/wjg.v20.i20.6102
  36. Fakih, M. G. 2015. Metastatic colorectal cancer: current state and future directions. J. Clin. Oncol. 33: 1809-1824.  https://doi.org/10.1200/JCO.2014.59.7633
  37. Ahmed, S., K. Johnson, O. Ahmed, and N. Iqbal. 2014. Advances in the management of colorectal cancer: from biology to treatment. Int. J. Colorectal Dis. 29: 1031-1042.  https://doi.org/10.1007/s00384-014-1928-5
  38. Ueno, H., N. Schmitt, E. Klechevsky, A. Pedroza-Gonzalez, T. Matsui, G. Zurawski, S. Oh, J. Fay, V. Pascual, J. Banchereau, and K. Palucka. 2010. Harnessing human dendritic cell subsets for medicine. Immunol. Rev. 234: 199-212.  https://doi.org/10.1111/j.0105-2896.2009.00884.x
  39. Obeid, J., Y. Hu, and C. L. Slingluff, Jr. 2015. Vaccines, adjuvants, and dendritic cell activators--current status and future challenges. Semin. Oncol. 42: 549-561.  https://doi.org/10.1053/j.seminoncol.2015.05.006
  40. Liu, K. J., C. C. Wang, L. T. Chen, A. L. Cheng, D. T. Lin, Y. C. Wu, W. L. Yu, Y. M. Hung, H. Y. Yang, S. H. Juang, and J. Whang-Peng. 2004. Generation of carcinoembryonic antigen (CEA)-specific T-cell responses in HLA-A*0201 and HLA-A*2402 HLA-A*2402  HLA-A*2402 late-stage colorectal cancer patients after vaccination with dendritic cells loaded with CEA peptides. Clin. Cancer Res. 10: 2645-2651.  https://doi.org/10.1158/1078-0432.CCR-03-0430
  41. Sakakibara, M., T. Kanto, M. Hayakawa, S. Kuroda, H. Miyatake, I. Itose, M. Miyazaki, N. Kakita, K. Higashitani, T. Matsubara, N. Hiramatsu, A. Kasahara, T. Takehara, and N. Hayashi. 2011. 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: 1565-1575.  https://doi.org/10.1007/s00262-011-1051-1
  42. Toh, H. C., W. W. Wang, W. K. Chia, P. Kvistborg, L. Sun, K. Teo, Y. P. Phoon, Y. Soe, S. H. Tan, S. W. Hee, K. F. Foo, S. Ong, W. H. Koo, M. B. Zocca, and M. H. Claesson. 2009. Clinical benefit of allogeneic melanoma cell lysate-pulsed autologous dendritic cell vaccine in MAGE-positive colorectal cancer patients. Clin. Cancer Res. 15: 7726-7736.  https://doi.org/10.1158/1078-0432.CCR-09-1537
  43. Burgdorf, S. K., A. Fischer, P. S. Myschetzky, S. B. Munksgaard, M. B. Zocca, M. H. Claesson, and J. Rosenberg. 2008. Clinical responses in patients with advanced colorectal cancer to a dendritic cell based vaccine. Oncol. Rep. 20: 1305-1311. 
  44. Hunyadi, J., C. Andras, I. Szabo, J. Szanto, K. Szluha, S. Sipka, P. Kovacs, A. Kiss, G. Szegedi, I. Altorjay, P. Sapy, P. Antal-Szalmas, L. Toth, G. Fazekas, and E. Rajnavolgyi. 2014. Autologous dendritic cell based adoptive immunotherapy of patients with colorectal cancer-A phase I-II study. Pathol. Oncol. Res. 20: 357-365.  https://doi.org/10.1007/s12253-013-9704-3
  45. Thompson, J. A., F. Grunert, and W. Zimmermann. 1991. Carcinoembryonic antigen gene family: molecular biology and clinical perspectives. J. Clin. Lab. Anal. 5: 344-366.  https://doi.org/10.1002/jcla.1860050510
  46. Kavanagh, B., A. Ko, A. Venook, K. Margolin, H. Zeh, M. Lotze, B. Schillinger, W. Liu, Y. Lu, P. Mitsky, M. Schilling, N. Bercovici, M. Loudovaris, R. Guillermo, S. M. Lee, J. Bender, B. Mills, and L. Fong. 2007. Vaccination of metastatic colorectal cancer patients with matured dendritic cells loaded with multiple major histocompatibility complex class I peptides. J. Immunother. 30: 762-772.  https://doi.org/10.1097/CJI.0b013e318133451c
  47. Rosenberg, S. A., B. S. Packard, P. M. Aebersold, D. Solomon, S. L. Topalian, S. T. Toy, P. Simon, M. T. Lotze, J. C. Yang, C. A. Seipp, C. Simpson, C. Carter, S. Bock, D. Schwartzentruber, J. P. Wei, and D. E. White. 1988. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N. Engl. J. Med. 319: 1676-1680.  https://doi.org/10.1056/NEJM198812223192527
  48. Dudley, M. E., J. R. Wunderlich, J. C. Yang, P. Hwu, D. J. Schwartzentruber, S. L. Topalian, R. M. Sherry, F. M. Marincola, S. F. Leitman, C. A. Seipp, L. Rogers-Freezer, K. E. Morton, A. Nahvi, S. A. Mavroukakis, D. E. White, and S. A. Rosenberg. 2002. A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma. J. Immunother. 25: 243-251.  https://doi.org/10.1097/00002371-200205000-00007
  49. Gardini, A., G. Ercolani, A. Riccobon, M. Ravaioli, L. Ridolfi, E. Flamini, R. Ridolfi, G. L. Grazi, A. Cavallari, and D. Amadori. 2004. Adjuvant, adoptive immunotherapy with tumor infiltrating lymphocytes plus interleukin-2 after radical hepatic resection for colorectal liver metastases: 5-year analysis. J. Surg. Oncol. 87: 46-52.  https://doi.org/10.1002/jso.20066
  50. Karlsson, M., P. Marits, K. Dahl, T. Dagoo, S. Enerback, M. Thorn, and O. Winqvist. 2010. Pilot study of sentinel-node-based adoptive immunotherapy in advanced colorectal cancer. Ann. Surg. Oncol. 17: 1747-1757.  https://doi.org/10.1245/s10434-010-0920-8
  51. Zhen, Y. H., X. H. Liu, Y. Yang, B. Li, J. L. Tang, Q. X. Zeng, J. Hu, X. N. Zeng, L. Zhang, Z. J. Wang, X. Y. Li, H. X. Ge, O. Winqvist, P. S. Hu, and J. Xiu. 2015. Phase I/II study of adjuvant immunotherapy with sentinel lymph node T lymphocytes in patients with colorectal cancer. Cancer Immunol. Immunother. 64: 1083-1093.  https://doi.org/10.1007/s00262-015-1715-3
  52. Parkhurst, M. R., J. C. Yang, R. C. Langan, M. E. Dudley, D. A. Nathan, S. A. Feldman, J. L. Davis, R. A. Morgan, M. J. Merino, R. M. Sherry, M. S. Hughes, U. S. Kammula, G. Q. Phan, R. M. Lim, S. A. Wank, N. P. Restifo, P. F. Robbins, C. M. Laurencot, and S. A. Rosenberg. 2011. T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol. Ther. 19: 620-626.  https://doi.org/10.1038/mt.2010.272
  53. Schmidt-Wolf, G. D., R. S. Negrin, and I. G. Schmidt-Wolf. 1997. Activated T cells and cytokine-induced CD3＋CD56＋ killer cells. Ann. Hematol. 74: 51-56.  https://doi.org/10.1007/s002770050257
  54. Franceschetti, M., A. Pievani, G. Borleri, L. Vago, K. Fleischhauer, J. Golay, and M. Introna. 2009. Cytokine-induced killer cells are terminally differentiated activated CD8 cytotoxic T-EMRA lymphocytes. Exp. Hematol. 37: 616-628 e612. 
  55. Verneris, M. R., J. Baker, M. Edinger, and R. S. Negrin. 2002. Studies of ex vivo activated and expanded CD8＋ NK-T cells in humans and mice. J. Clin. Immunol. 22: 131-136.  https://doi.org/10.1023/A:1015415928521
  56. Pievani, A., G. Borleri, D. Pende, L. Moretta, A. Rambaldi, J. Golay, and M. Introna. 2011. Dual-functional capability of CD3＋CD56＋ CIK cells, a T-cell subset that acquires NK function and retains TCR-mediated specific cytotoxicity. Blood 118: 3301-3310.  https://doi.org/10.1182/blood-2011-02-336321
  57. Jakel, C. E., and I. G. Schmidt-Wolf. 2014. An update on new adoptive immunotherapy strategies for solid tumors with cytokine-induced killer cells. Expert Opin. Biol. Ther. 14: 905-916.  https://doi.org/10.1517/14712598.2014.900537
  58. Zhu, Y., H. Zhang, Y. Li, J. Bai, L. Liu, Y. Liu, Y. Qu, and X. Qu. 2013. Efficacy of postoperative adjuvant transfusion of cytokine-induced killer cells combined with chemotherapy in patients with colorectal cancer. Cancer Immunol. Immunother. 62: 1629-1635.  https://doi.org/10.1007/s00262-013-1465-z
  59. Zhu, H., X. Yang, J. Li, Y. Ren, T. Zhang, C. Zhang, J. Zhang, J. Li, and Y. Pang. 2014. Immune response, safety, and survival and quality of life outcomes for advanced colorectal cancer patients treated with dendritic cell vaccine and cytokine-induced killer cell therapy. Biomed Res Int 2014: 603871. 
  60. Gao, D., C. Li, X. Xie, P. Zhao, X. Wei, W. Sun, H. C. Liu, A. T. Alexandrou, J. Jones, R. Zhao, and J. J. Li. 2014. Autologous tumor lysate-pulsed dendritic cell immunotherapy with cytokine-induced killer cells improves survival in gastric and colorectal cancer patients. PLoS One 9: e93886. 
  61. Leibovitz, A., J. C. Stinson, W. B. McCombs, 3rd, C. E. McCoy, K. C. Mazur, and N. D. Mabry. 1976. Classification of human colorectal adenocarcinoma cell lines. Cancer Res. 36: 4562-4569. 
  62. Ramirez, R., R. Solana, J. Carracedo, M. C. Alonso, and J. Pena. 1992. Mechanisms involved in NK resistance induced by interferon-gamma. Cell. Immunol. 140: 248-256.  https://doi.org/10.1016/0008-8749(92)90191-Q
  63. Esin, E., and S. Yalcin. 2016. Maintenance strategy in metastatic colorectal cancer: A systematic review. Cancer Treat. Rev. 42: 82-90.  https://doi.org/10.1016/j.ctrv.2015.10.012
  64. Ko, J. J., H. F. Kennecke, H. J. Lim, D. J. Renouf, S. Gill, R. Woods, C. Speers, and W. Y. Cheung. 2015. Reasons for underuse of adjuvant chemotherapy in elderly patients with stage III colon cancer. Clin. Colorectal Cancer. doi: 10.1016/j.clcc.2015.09.002. 
  65. Morse, M. A., D. Niedzwiecki, J. L. Marshall, C. Garrett, D. Z. Chang, M. Aklilu, T. S. Crocenzi, D. J. Cole, S. Dessureault, A. C. Hobeika, T. Osada, M. Onaitis, B. M. Clary, D. Hsu, G. R. Devi, A. Bulusu, R. P. Annechiarico, V. Chadaram, T. M. Clay, and H. K. Lyerly. 2013. A randomized phase II study of immunization with dendritic cells modified with poxvectors encoding CEA and MUC1 compared with the same poxvectors plus GM-CSF for resected metastatic colorectal cancer. Ann. Surg. 258: 879-886.  https://doi.org/10.1097/SLA.0b013e318292919e
  66. Morse, M. A., T. M. Clay, A. C. Hobeika, T. Osada, S. Khan, S. Chui, D. Niedzwiecki, D. Panicali, J. Schlom, and H. K. Lyerly. 2005. Phase I study of immunization with dendritic cells modified with fowlpox encoding carcinoembryonic antigen and costimulatory molecules. Clin. Cancer Res. 11: 3017-3024.  https://doi.org/10.1158/1078-0432.CCR-04-2172
  67. Matsuda, K., T. Tsunoda, H. Tanaka, Y. Umano, H. Tanimura, I. Nukaya, K. Takesako, and H. Yamaue. 2004. Enhancement of cytotoxic T-lymphocyte responses in patients with gastrointestinal malignancies following vaccination with CEA peptide-pulsed dendritic cells. Cancer Immunol. Immunother. 53: 609-616. https://doi.org/10.1007/s00262-003-0491-7