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Overcome the Impairment of NK Cells for Icon and Antibody Immunotherapy of Cancer

  1. 1 Department of Surgery, The Ohio State University College of Medicine, Columbus, USA
Journal of Immune Based Therapies, Vaccines and Antimicrobials·Volume 02, Issue 1·Pages 1–8·Published 25 January 2013·DOI10.4236/jibtva.2013.21001
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Abstract

Natural killer (NK) cells play an important role in innate immunity and in mediating antibody and Icon (an antibody-like factor VII/IgG1 Fc immunoconjugate, which, to our best knowledge, was the first therapeutic agent for dual targeting of both the tumor cells and tumor angiogenic endothelial cells) for cancer immunotherapy. However, a common yet often neglected observation and challenge in antibody immunotherapy is that NK cells are often impaired in cancer patients. Here we hypothesize that the impairment of NK cells significantly contributes to host resistance to antibody immunotherapy for cancer. In order for antibody and Icon to achieve their optimal therapeutic efficacy, we briefly reviewed the current strategies to enhance NK activity, including infusion of cytokines, vaccines or NK cells, and the use of dietary supplements. Moreover, from our point of view we identified some remaining challenges and propose to combine these NK-enhancing strategies with Icon or antibody to overcome NK impairment and ultimately to optimize the efficacy of Icon and antibody immunotherapy for cancer.

KeywordsNatural Killer CellsAntibodyCancer ImmunotherapyIconDietary Supplements
  1. R. B. Herberman, “Cancer Immunotherapy with Natural Killer Cells,” Seminars in Oncology, Vol. 29, No. 3, 2002, pp. 27-30. doi:10.1053/sonc.2002.33079
  2. T. L. Whiteside, N. L. Vujanovic and R. B. Herberman, “Natural Killer Cells and Tumor Therapy,” Current Topics in Microbiology and Immunology, Vol. 230, 1998, pp. 221-244. doi:10.1007/978-3-642-46859-9_13
  3. S. S. Farag, T. Fehniger, L. Ruggeri, A. Velardi and M. A. Caligiuri, “Natural Killer Cells: Biology and Application in Stem-Cell Transplantation,” Cytotherapy, Vol. 4, No. 5, 2002, pp. 445-446. doi:10.1080/146532402320776134
  4. P. H. Basse, T. L. Whiteside and R. B. Herberman, “Cancer Immunotherapy with Interleukin-2-Activated Natural Killer Cells,” Molecular Biotechnology, Vol. 21, No. 2, 2002, pp. 161-170. doi:10.1385/MB:21:2:161
  5. P. H. Basse, T. L. Whiteside and R. B. Herberman, “Use of Activated Natural Killer Cells for Tumor Immunotherapy in Mouse and Human,” Methods in Molecular Biology, Vol. 121, 2000, pp. 81-94.
  6. L. Yan, K. Hsu and R. A. Beckman, “Antibody-Based Therapy for Solid Tumors,” Cancer Journal, Vol. 14, No. 3, 2008, pp. 178-183. doi:10.1097/PPO.0b013e318172d71a
  7. Z. Hu, “Factor VII-Targeted Photodynamic Therapy for Breast Cancer and Its Therapeutic Potential for Other Solid Cancers and Leukemia, Breast Cancer—Current and Alternative Therapeutic Modalities, Esra Gunduz and Mehmet Gunduz,” 2011. http://www.intechopen.com/articles/show/title/factor-vii-tageted-photodynamic-therapy-for-breast-cancer-and-its-therapeutic-potential-for-other-s
  8. Z. Hu, Y. Sun and A. Garen, “Targeting Tumor Vasculature Endothelial Cells and Tumor Cells for Immunotherapy of Human Melanoma in a Mouse Xenograft Model,” Proceedings of the National Academy of Sciences of United States of America, Vol. 96, No. 14, 1999, pp. 8161-8166.
  9. Z. Hu and A. Garen, “Intratumoral Injection of Adenoviral Vectors Encoding Tumor-Targeted Immunoconjugates for Cancer Immunotherapy,” Proceedings of the National Academy of Sciences of United States of America, Vol. 97, No. 16, 2000, pp. 9221-9225. doi:10.1073/pnas.97.16.9221
  10. Z. Hu and A. Garen “Targeting Tissue Factor on Tumor Vascular Endothelial Cells and Tumor Cells for Immunotherapy in Mouse Models of Prostatic Cancer,” Proceedings of the National Academy of Sciences of United States of America, Vol. 98, No. 21, 2001, Article ID:. 12180. doi:10.1073/pnas.201420298
  11. Z. Hu and J. Li, “Natural Killer Cells Are Crucial for the Efficacy of Icon (Factor VII/Human IgG1 Fc) Immunotherapy in Human Tongue Cancer,” BMC Immunology, Vol. 11, 2010, p. 49. doi:10.1186/1471-2172-11-49
  12. J. Contrino, G. Hair, D. L. Kreutzer and F. R. Rickles, “In Situ Detection of Tissue Factor in Vascular Endothelial Cells: Correlation with the Malignant Phenotype of Human Breast Disease,” Nature Medicine Vol. 2, No. 2, 1996, pp. 209-215. doi:10.1038/nm0296-209
  13. Y. Tang, P. Borgstrom, J. Maynard, J. Koziol, Z. Hu, A. Garen and A. Deisseroth, “Mapping of Angiogenic Markers for Targeting of Vectors to Tumor Vascular Endothelial Cells,” Cancer Gene Therapy, Vol. 14, No. 4, 2007, pp. 346-353. doi:10.1038/sj.cgt.7701030
  14. E. Cocco, Z. Hu, C. E. Richter, S. Bellone, F. Casagrande, M. Bellone, P. Todeschini, G. Krikun, D. A. Silasi, M. Azodi, P. E. Schwartz, T. J. Rutherford, N. Buza, S. Pecorelli, C. J. Lockwood and A. D. Santin, “hI-con1, a factor VII-IgGFc Chimeric Protein Targeting Tissue Factor for Immunotherapy of Uterine Serous Papillary Carcinoma,” British Journal of Cancer, Vol. 103, No. 6, 2010, pp. 812-819. doi:10.1038/sj.bjc.6605760
  15. P. S. Bora, Z. Hu, T. H. Tezel, J. H. Sohn, S. G. Kang, J. M. Cruz, N. S. Bora, A. Garen and H. J. Kaplan, “Immunotherapy for Choroidal Neovascularization in a Laser- Induced Mouse Model Simulating Exudative (Wet) Macular Degeneration,” Proceedings of the National Academy of Sciences of United States of America Vol. 100, No. 5, 2003, pp. 2679-2684. doi:10.1073/pnas.0438014100
  16. T. H. Tezel, E. Bodek, K. Sonmez, S. Kaliappan, H. J. Kaplan, Z. Hu and A. Garen, “Targeting Tissue Factor for Immunotherapy of Choroidal Neovascularization by Intravitreal Delivery of Factor VII-Fc Chimeric Antibody,” Ocular Immunology and Inflammation, Vol. 15, No. 1, 2007, pp. 3-10. doi:10.1080/09273940601147760
  17. G. Krikun, Z. Hu, K. Osteen, K. L. Bruner-Tran, F. Schatz, H. S. Taylor, P. Toti, F. Arcuri, W. Konigsberg, A. Garen, C. J. Booth and C. J. Lockwood, “The Immunoconjugate ‘Icon’ Targets Aberrantly Expressed Endothelial Tissue Factor Causing Regression of Endometriosis,” The American Journal of Pathology, Vol. 176, No. 2, 2010, pp. 1050-1056. doi:10.2353/ajpath.2010.090757
  18. P. Carter, L. Presta, C. M. Gorman, J. B. Ridgway, D. Henner, W. L. Wong, A. M. Rowland, C. Kotts, M. E. Carver and H. M. Shepard, “Humanization of an Anti- P185HER2 Antibody for Human Cancer Therapy,” Proceedings of the National Academy of Sciences of United States of America, Vol. 89, No. 10, 1992, pp. 4285- 4289. doi:10.1073/pnas.89.10.4285
  19. M. E. Reff, K. Carner, K. S. Chambers, P. C. Chinn, J. E. Leonard, R. Raab, R. A. Newman, N. Hanna and D. R. Anderson, “Depletion of B Cells in Vivo by a Chimeric Mouse Human Monoclonal Antibody to CD20,” Blood, Vol. 83, No. 2, 1994, pp. 435-445.
  20. J. Kurai, H. Chikumi, K. Hashimoto, K. Yamaguchi, A. Yamasaki, T. Sako, H. Touge, H. Makino, M. Takata, M. Miyata, M. Nakamoto, N. Burioka and E. Shimizu, “Antibody-Dependent Cellular Cytotoxicity Mediated by Cetuximab against Lung Cancer Cell Lines,” Clinical Cancer Research, Vol. 13, No. 5, 2007, pp. 1552-1561. doi:10.1158/1078-0432.CCR-06-1726
  21. R. Kiessling, E. Klein, H. Pross and H. Wigzell, “‘Natural’ Killer Cells in The Mouse. II. Cytotoxic Cells with Specificity for Mouse Moloney Leukemia Cells. Characteristics of the Killer Cell,” European Journal of Immunology, Vol. 5, No. 2, 1975, pp. 117-121. doi:10.1002/eji.1830050209
  22. R. B. Herberman, M. E. Nunn, H. T. Holden and D. H. Lavrin, “Natural Cytotoxic Reactivity of Mouse Lymphoid Cells against Syngeneic and Allogeneic Tumors. II. Characterization of Effector Cells,” International Journal of Cancer, Vol. 16, No. 2, 1975, pp. 230-239. doi:10.1002/ijc.2910160205
  23. J. Thornthwaite, H. Shah, P. Shah and H. Respess, “The Natural Killer Cell: A Historical Perspective and the Use of Supplements to Enhance NKC Activity,” Journal of Immune Based Therapies, Vaccines and Antimicrobials, Vol. 1, No. 3, 2012, pp. 21-51. doi:10.4236/jibtva.2012.13004
  24. R. B. Herberman, J. Djeu, H. D. Kay, J. R. Ortaldo, C. Riccardi, G. D. Bonnard, H. T. Holden, R. Fagnani, A. Santoni and P. Puccetti, “Natural Killer Cells: Characteristics and Regulation of Activity,” Immunological Reviews, Vol. 44, No. 1, 1979, pp. 43-70. doi:10.1111/j.1600-065X.1979.tb00267.x
  25. R. Kiessling, K. Wasserman, S. Horiguchi, K. Kono, J. Sjoberg, P. Pisa and M. Petersson, “Tumor-Induced Immune Dysfunction,” Cancer Immunology Immunotherapy, Vol. 48, No. 7, 1999, pp. 353-362. doi:10.1007/s002620050586
  26. T. Sutlu and E. Alici, “Natural Killer Cell-Based Immunotherapy in Cancer: Current Insights and Future Prospects,” Journal of Internal Medicine, Vol. 266, No. 2, 2009, pp. 154-181. doi:10.1111/j.1365-2796.2009.02121.x
  27. S. P. Schantz, B. W. Brown, E. Lira, D. L. Taylor and N. Beddingfield, “Evidence for the Role of Natural Immunity in the Control of Metastatic Spread of Head and Neck Cancer,” Cancer Immunology Immunotherapy, Vol. 25, No. 2, 1987, pp. 141-148. doi:10.1007/BF00199955
  28. K. Vinzenz, M. Matejka, G. Watzek, H. Porteder, N. Neuhold and M. Micksche, “Modulation of NK Activity in Regional Lymph Nodes by Preoperative Immunotherapy with OK-432 in Patients with Cancer of the Oral Cavity,” Cancer Detection and Prevention, Vol. 1, 1987, pp. 463- 475.
  29. K. A. Varker, C. E. Terrell, M. Welt, S. Suleiman, L. Thornton, B. L. Andersen and W. E. Carson, “Impaired Natural Killer Cell Lysis in Breast Cancer Patients with High Levels of Psychological Stress Is Associated with Altered Expression of Killer Immunoglobin-Like Receptors,” The Journal of Surgical Research, Vol. 139, No. 1, 2007, pp. 36-44. doi:10.1016/j.jss.2006.08.037
  30. K. Kono, A. Takahashi, F. Ichihara, H. Sugai, H. Fujii and Y. Matsumoto, “Impaired Antibody-Dependent Cellular Cytotoxicity Mediated by Herceptin in Patients with Gastric Cancer,” Cancer Research, Vol. 62, No. 20, 2002, pp. 5813-5817.
  31. Y. Kawaguchi, K. Kono, K. Mimura, F. Mitsui, H. Sugai, H. Akaike and H. Fujii, “Targeting EGFR and HER-2 with Cetuximab- and Trastuzumab-Mediated Immunotherapy in Oesophageal Squamous Cell Carcinoma,” British Journal of Cancer, Vol. 97, No. 4, 2007, pp. 494- 501. doi:10.1038/sj.bjc.6603885
  32. Y. Kawaguchi, K. Kono, K. Mimura, H. Sugai, H. Akaike and H. Fujii, “Cetuximab Induce Antibody-Dependent Cellular Cytotoxicity against EGFR-Expressing Esophageal Squamous Cell Carcinoma,” International Journal of Cancer, Vol. 120, No. 4, 2007, pp. 781-787. doi:10.1002/ijc.22370
  33. M. R. Pillai, P. Balaram, T. Abraham, T. K. Padmanabhan and M. K. Nair, “Natural Cytotoxicity and Serum Blocking in Malignant Cervical Neoplasia,” American Journal of Reproductive Immunology, Vol. 16, No. 4, 1988, pp. 159-162.
  34. T. L. Ratliff, R. E. McCool and W. J. Catalona, “Antibody-Dependent and Spontaneous Lympholysis in Urologic Cancer Patients,” British Journal of Cancer, Vol. 39, No. 6, 1979, pp. 667-675. doi:10.1038/bjc.1979.118
  35. C. D. Platsoucas, G. Fernandes, S. L. Gupta, S. Kempin, B. Clarkson, R. A. Good and S. Gupta, “Defective Spontaneous and Antibody-Dependent Cytotoxicity Mediated by E-Rosette-Positive and E-Rosette-Negative Cells in Untreated Patients with Chronic Lymphocytic Leukemia: Augmentation by in Vitro Treatment with Interferon,” The Journal of Immunology, Vol. 125, No. 3, 1980, pp. 1216-1223.
  36. H. W. Ziegler, N. E. Kay and J. M. Zarling, “Deficiency of Natural Killer Cell Activity in Patients with Chronic Lymphocytic Leukemia,” International Journal of Cancer, Vol. 27, No. 3, 1981, pp. 321-327. doi:10.1002/ijc.2910270310
  37. N. E. Kay and J. M. Zarling, “Impaired Natural Killer Activity in Patients with Chronic Lymphocytic Leukemia Is Associated with a Deficiency of Azurophilic Cytoplasmic Granules in Putative NK Cells,” Blood, Vol. 63, No. 2, 1984, pp. 305-309.
  38. H. Matsuzaki, T. Kagimoto, T. Oda, F. Kawano and K. Takatsuki, “Natural Killer Activity and Antibody-Dependent Cell-Mediated Cytotoxicity in Multiple Myeloma,” Japanese Journal of Clinical Oncology, Vol. 15, No. 4, 1985, pp. 611-617.
  39. J. W. Albright and J. F. Albright, “Age-Associated Impairment of Murine Natural Killer Activity,” Proceedings of the National Academy of Sciences of United States of America, Vol. 80, No. 20, 1983, pp. 6371-6375. doi:10.1073/pnas.80.20.6371
  40. K. Dorshkind, S. B. Pollack, M. J. Bosma and R. A. Phillips, “Natural Killer (NK) Cells Are Present in Mice with Severe Combined Immunodeficiency (Scid),” The Journal of Immunology, Vol. 134, No. 6, 1985, pp. 3798- 3801.
  41. J. Roder and A. Duwe, “The Beige Mutation in the Mouse Selectively Impairs Natural Killer Cell Function,” Nature, Vol. 278, No. 5703, 1979, pp. 451-453. doi:10.1038/278451a0
  42. J. R. MacDougall, B. A. Croy, C. Chapeau and D. A. Clark, “Demonstration of a Splenic Cytotoxic Effector Cell in Mice of Genotype SCID/SCID.BG/BG,” Cellular Immunology, Vol. 130, No. 1, 1990, pp. 106-117.
  43. R. Nahta and F. J. Esteva, “HER2 Therapy: Molecular Mechanisms of Trastuzumab Resistance,” Breast Cancer Research, Vol. 8, No. 6, 2006, p. 215. doi:10.1186/bcr1612
  44. S. Varchetta, N. Gibelli, B. Oliviero, E. Nardini, R. Gennari, G. Gatti, L. S. Silva, L. Villani, E. Tagliabue, S. Menard, A. Costa and F. F. Fagnoni, “Elements Related to Heterogeneity of Antibody-Dependent Cell Cytotoxicity in Patients under Trastuzumab Therapy for Primary Operable Breast Cancer Overexpressing Her2,” Cancer Research, Vol. 67, No. 24, 2007, pp. 11991-11999. doi:10.1158/0008-5472.CAN-07-2068
  45. M. Ostensen and O. Forre, “Modulation of Human Natural Killer Cell Function by Cytokines and Rheumatic Disease,” Scandinavian Journal of Rheumatology. Supplement, Vol. 17, No. s76, 1988, pp. 183-188. doi:10.3109/03009748809102968
  46. M. J. Brunda, “Interleukin-12,” Journal of Leukocyte Biology, Vol. 55, No. 2, 1994, pp. 280-288.
  47. L. Oleksowicz and J. P. Dutcher, “A Review of the New Cytokines: IL-4, IL-6, IL-11, and IL-12,” American Journal of Therapeutics, Vol. 1, No. 2, 1994, pp. 107-115. doi:10.1097/00045391-199408000-00002
  48. M. Cheng, J. Zhang, W. Jiang, Y. Chen and Z. Tian, “Natural Killer Cell Lines in Tumor Immunotherapy,” Frontiers of Medicine, Vol. 6, No. 1, 2012, pp. 56-66. doi:10.1007/s11684-012-0177-7
  49. A. S. Fauci, S. A. Rosenberg, S. A. Sherwin, C. A. Dinarello, D. L. Longo and H. C. Lane, “NIH Conference. Immunomodulators in Clinical Medicine,” Annals of Internal Medicine, Vol. 106, No. 3, 1987, pp. 421-433.
  50. M. T. Lotze, M. C. Custer, E. S. Bolton, E. A. Wiebke, Y. Kawakami and S. A. Rosenberg, “Mechanisms of Immunologic Antitumor Therapy: Lessons from the Laboratory and Clinical Applications,” Human Immunology, Vol. 28, No. 2, 1990, pp. 198-207. doi:10.1016/0198-8859(90)90020-P
  51. Z. K. Ballas, “Modulation of NK Cell Activity by CpG Oligodeoxynucleotides,” Immunology Research, Vol. 39, No. 1-3, 2007, pp. 15-21. doi:/10.1007/s12026-007-0066-3
  52. M. H. Shah, R. A. Baiocchi, T. A. Fehniger, V. P. Khatri, M. Gould, B. Poiesz, Z. P. Bernstein and M. A. Caligiuri, “Cytokine Replacement in Patients with HIV-1 Non- Hodgkin’s Lymphoma: The Rationale for Low-Dose Interleukin-2 Therapy,” The Cancer Journal from Scientific American, Vol. 6, No. S1, 2000, pp. S45-S51.
  53. N. S. Bhave and W. E. Carson, 3rd, “Immune Modulation with Interleukin-21,” Annals of the New York Academy of Sciences, Vol. 1182, 2009, pp. 39-46. doi:/10.1111/j.1749-6632.2009.05071.x
  54. J. Copier and A. Dalgleish, “Whole-Cell Vaccines: A Failure or a Success Waiting to Happen?” Current Opinion in Molecular Therapeutics, Vol. 12, No. 1, 2010, pp. 14-20.
  55. J. P. Siegel and R. K. Puri, “Interleukin-2 Toxicity,” Journal of Clinical Oncology, Vol. 9, No. 4, 1991, pp. 694- 704.
  56. K. Nakagawa, F. N. Miller, D. E. Sims, A. B. Lentsch, M. Miyazaki and M. J. Edwards, “Mechanisms of Interleukin-2-Induced Hepatic Toxicity,” Cancer Research, Vol. 56, No. 3, 1996, pp. 507-510.
  57. R. Passalacqua, C. Buzio, S. Buti, C. Porta, R. Labianca, D. Pezzuolo, R. Camisa, R. Sabbatini, L. Benecchi, C. Messina, R. Cengarle, A. Vaglio, M. Dalla Chiesa, G. Tomasello and C. Caminiti, “Phase III, Randomised, Multicentre Trial of Maintenance Immunotherapy with Low- Dose Interleukin-2 and Interferon-Alpha for Metastatic Renal Cell Cancer,” Cancer Immunology, Immunotherapy, Vol. 59, No. 4, 2010, pp. 553-561. doi:/10.1007/s00262-009-0773-9
  58. J. Lister, W. B. Rybka, A. D. Donnenberg, M. deMagalhaes-Silverman, S. M. Pincus, E. J. Bloom, E. M. Elder, E. D. Ball and T. L. Whiteside, “Autologous Peripheral Blood Stem Cell Transplantation and Adoptive Immunotherapy with Activated Natural Killer Cells in the Immediate Posttransplant Period,” Clinical Cancer Research, Vol. 1, No. 6, 1995, pp. 607-614.
  59. M. deMagalhaes-Silverman, A. Donnenberg, B. Lembersky, E. Elder, J. Lister, W. Rybka, T. Whiteside and E. Ball, “Posttransplant Adoptive Immunotherapy with Activated Natural Killer Cells in Patients with Metastatic Breast Cancer,” Journal of Immunotherapy, Vol. 23, No. 1, 2000, pp. 154-160. doi:/10.1097/00002371-200001000-00018
  60. V. Bachanova, L. J. Burns, D. H. McKenna, J. Curtsinger, A. Panoskaltsis-Mortari, B. R. Lindgren, S. Cooley, D. Weisdorf and J. S. Miller, “Allogeneic Natural Killer Cells for Refractory Lymphoma,” Cancer Immunology, Immunotherapy, Vol. 59, No. 11, 2010, pp. 1739-1744. doi:/10.1007/s00262-010-0896-z
  61. E. Ishikawa, K. Tsuboi, K. Saijo, H. Harada, S. Takano, T. Nose and T. Ohno, “Autologous Natural Killer Cell Therapy for Human Recurrent Malignant Glioma,” Anticancer Research, Vol. 24, No. 3b, 2004, pp. 1861-1871.
  62. M. R. Parkhurst, J. P. Riley, M. E. Dudley and S. A. Rosenberg, “Adoptive Transfer of Autologous Natural Killer Cells Leads to High Levels of Circulating Natural Killer Cells but Does Not Mediate Tumor Regression,” Clinical Cancer Research, Vol. 17, No. 19, 2011, pp. 6287-6297.doi:/10.1158/1078-0432.CCR-11-1347
  63. D. H. McKenna Jr., D. Sumstad, N. Bostrom, D. M. Kadidlo, S. Fautsch, S. McNearney, R. Dewaard, P. B. Mc- Glave, D. J. Weisdorf, J. E. Wagner, J. McCullough and J. S. Miller, “Good Manufacturing Practices Production of Natural Killer Cells for Immunotherapy: A Six-Year Single-Institution Experience,” Transfusion, Vol. 47, No. 3, 2007, pp. 520-528. doi:/10.1111/j.1537-2995.2006.01145.x
  64. Y. P. Tang, P. G. Li, M. Kondo, H. P. Ji, Y. Kou and B. Ou, “Effect of a Mangosteen Dietary Supplement on Human Immune Function: A Randomized, Double-Blind, Placebo-Controlled Trial,” Journal of Medicinal Food, Vol. 12, No. 4, 2009, pp. 755-763. doi:/10.1089/jmf.2008.0204
  65. B. G. Jung, N. T. Toan, S. J. Cho, J. H. Ko, Y. K. Jung and B. J. Lee, “Dietary Aluminosilicate Supplement Enhances Immune Activity in Mice and Reinforces Clearance of Porcine Circovirus Type 2 in Experimentally Infected Pigs,” Veterinary Microbiology, Vol. 143, No. 2-4, 2010, pp. 117-125. doi:/10.1016/j.vetmic.2009.11.009
  66. Y. Li, T. Zhang, H. Korkaya, S. Liu, H. F. Lee, B. Newman, Y. Yu, S. G. Clouthier, S. J. Schwartz, M. S. Wicha and D. Sun, “Sulforaphane, a Dietary Component of Broccoli/Broccoli Sprouts, Inhibits Breast Cancer Stem Cells,” Clinical Cancer Research, Vol. 16, No. 9, 2010, pp. 2580-2590. doi:/10.1158/1078-0432.CCR-09-2937
  67. K. R. Landis-Piwowar, C. Huo, D. Chen, V. Milacic, G. Shi, T. H. Chan and Q. P. Dou, “A Novel Prodrug of the Green Tea Polyphenol (?)-Epigallocatechin-3-Gallate as a Potential Anticancer Agent,” Cancer Research, Vol. 67, No. 9, 2007, pp. 4303-4310. doi:/10.1158/0008-5472.CAN-06-4699
  68. A. P. Sommer, D. Zhu and T. Scharnweber, “Extraordinary Anticancer Effect of Green Tea and Red Light,” Photomedicine and Laser Surgery, Vol. 28, No. 3, 2010, pp. 429-430. doi:/10.1089/pho.2009.2706
  69. D. M. Morre and D. J. Morre, “Anticancer Activity of Grape and Grape Skin Extracts Alone and Combined with Green Tea Infusions,” Cancer Letters, Vol. 238, No. 2, 2006, pp. 202-209. doi:/10.1016/j.canlet.2005.07.011
  70. T. Pannellini, M. Iezzi, M. Liberatore, F. Sabatini, S. Iacobelli, C. Rossi, S. Alberti, C. Di Ilio, P. Vitaglione, V. Fogliano and M. Piantelli, “A Dietary Tomato Supplement Prevents Prostate Cancer in TRAMP Mice,” Cancer Prevention Research, Vol. 3, No. 10, 2010, pp. 1284- 1291. doi:/10.1158/1940-6207.CAPR-09-0237
  71. R. Cooper, D. J. Morre and D. M. Morre, “Medicinal Benefits of Green Tea: Part II. Review of Anticancer Properties,” The Journal of Alternative and Complementary Medicine, Vol. 11, No. 4, 2005, pp. 639-652. doi:/10.1089/acm.2005.11.639
  72. L. M. Dong, A. R. Kristal, U. Peters, J. M. Schenk, C. A. Sanchez, P. S. Rabinovitch, P. L. Blount, R. D. Odze, K. Ayub, B. J. Reid and T. L. Vaughan, “Dietary Supplement Use and Risk of Neoplastic Progression in Esophageal Adenocarcinoma: A Prospective Study,” Nutrition and Cancer, Vol. 60, No. 1, 2008, pp. 39-48. doi:/10.1080/01635580701586762
  73. M. F. Miller, K. M. Bellizzi, M. Sufian, A. H. Ambs, M. S. Goldstein and R. Ballard-Barbash, “Dietary Supplement Use in Individuals Living with Cancer and Other Chronic Conditions: A Population-Based Study,” Journal of the American Dietetic Association, Vol. 108, No. 3, 2008, pp. 483-494. doi:/10.1016/j.jada.2007.12.005
  74. P. Miller, W. Demark-Wahnefried, D. C. Snyder, R. Sloane, M. C. Morey, H. Cohen, S. Kranz, D. C. Mitchell and T. J. Hartman, “Dietary Supplement Use among Elderly, Long-Term Cancer Survivors,” Journal of Cancer Survivorship, Vol. 2, No. 3, 2008, pp. 138-148. doi:/10.1007/s11764-008-0060-3
  75. C. L. Van Patten, J. G. de Boer and E. S. Tomlinson Guns, “Diet and Dietary Supplement Intervention Trials for the Prevention of Prostate Cancer Recurrence: A Review of the Randomized Controlled Trial Evidence,” Journal of Urology, Vol. 180, No. 6, 2008, pp. 2314-2321.
  76. P. E. Miller, J. J. Vasey, P. F. Short and T. J. Hartman, “Dietary Supplement Use in Adult Cancer Survivors,” Oncology Nursing Forum, Vol. 36, No. 1, 2009, pp. 61- 68. doi:/10.1188/09.ONF.61-68
  77. M. L. Neuhouser, M. J. Barnett, A. R. Kristal, C. B. Ambrosone, I. B. King, M. Thornquist and G. G. Goodman, “Dietary Supplement Use and Prostate Cancer Risk in the Carotene and Retinol Efficacy Trial,” Cancer Epidemiology, Biomarkers & Prevention, Vol. 18, No. 8, 2009, pp. 2202-2206. doi:/10.1158/1055-9965.EPI-09-0013
  78. M. A. Moyad and L. H. Klotz, “Statin Clinical Trial (REALITY) for Prostate Cancer: An over 15-Year Wait Is Finally over Thanks to a Dietary Supplement,” Urologic Clinics of North America, Vol. 38, No. 3, 2011, pp. 325-331. doi:/10.1016/j.ucl.2011.05.002
  79. J. Saquib, C. L. Rock, L. Natarajan, N. Saquib, V. A. Newman, R. E. Patterson, C. A. Thomson, W. K. Al-Delaimy and J. P. Pierce, “Dietary Intake, Supplement Use, and Survival among Women Diagnosed with Early-Stage Breast Cancer,” Nutrition and Cancer, Vol. 63, No. 3, 2011, pp. 327-333. doi:/10.1080/01635581.2011.535957
  80. A. Westerlund, G. Steineck, K. Balter, P. Stattin, H. Gronberg and M. Hedelin, “Dietary Supplement Use Patterns in Men with Prostate Cancer: The Cancer Prostate Sweden Study,” Annals of Oncology, Vol. 22, No. 4, 2011, pp. 967-972. doi:/10.1093/annonc/mdq456
  81. P. Gardiner, D. N. Sarma, T. Low Dog, M. L. Barrett, M. L. Chavez, R. Ko, G. B. Mahady, R. J. Marles, L. S. Pellicore and G. I. Giancaspro, “The State of Dietary Supplement Adverse Event Reporting in the United States,” Pharmacoepidemiol Drug Safety, Vol. 17, No. 10, 2008, pp. 962-970. doi:/10.1002/pds.1627
  82. M. L. Hardy, “Dietary Supplement Use in Cancer Care: Help or Harm,” Hematology/Oncology Clinics of North America, Vol. 22, No. 4, 2008, pp. 581-617. doi:/10.1016/j.hoc.2008.04.012
  83. V. J. Navarro, “Herbal and Dietary Supplement Hepatotoxicity,” Seminars in Liver Disease, Vol. 29, No. 4, 2009, pp. 373-382. doi:/10.1055/s-0029-1240006
  84. R. K. Miller, C. Celestino, G. I. Giancaspro and R. L. Williams, “FDA’s Dietary Supplement Cgmps: Standards without Standardization,” Food and Drug, Law Journal, Vol. 63, No. 4, 2008, pp. 929-942. doi:/10.1038/287047a0
  85. G. Dennert, “Cloned Lines of Natural Killer Cells,” Nature, Vol. 287, No. 5777, 1980, pp. 47-49.
  86. M. Manoussaka, A. Georgiou, B. Rossiter, S. Shrestha, J. A. Toomey, P. V. Sivakumar, M. Bennett, V. Kumar and C. G. Brooks, “Phenotypic and Functional Characterization of Long-Lived NK Cell Lines of Different Maturational Status Obtained from Mouse Fetal Liver,” The Journal of Immunology, Vol. 158, No. 1, 1997, pp. 112- 119.
  87. F. M. Karlhofer, M. M. Orihuela and W. M. Yokoyama, “Ly-49-Independent Natural Killer (NK) Cell Specificity, Revealed by NK Cell Clones Derived from P53-Deficient Mice,” The Journal of Experimental Medicine, Vol. 181, No. 5, 1995, pp. 1785-1795. doi:/10.1084/jem.181.5.1785
  88. Q. Vos, J. R. Ortaldo, M. Conan-Cibotti, M. D. Vos, H. A. Young, S. K. Anderson, K. Witherspoon, I. Prager, C. M. Snapper and J. J. Mond, “Phenotypic and Functional Characterization of a Panel of Cytotoxic Murine NK Cell Clones That Are Heterogeneous in Their Enhancement of Ig Secretion in Vitro,” International Immunology, Vol. 10, No. 8, 1998, pp. 1093-1101. doi:/10.1093/intimm/10.8.1093
  89. S. Iizuka, T. Kaifu, A. Nakamura, M. Obinata and T. Takai, “Establishment and Functional Characterization of Novel Natural Killer Cell Lines Derived from a Temperature-Sensitive SV40 Large T Antigen Transgenic Mouse,” The Journal of Biochemistry, Vol. 140, No. 2, 2006, pp. 255-265. doi:/10.1093/jb/mvj153
  90. Y. Isobe, K. Sugimoto, L. Yang, K. Tamayose, M. Egashira, T. Kaneko, K. Takada and K. Oshimi, “Epstein- Barr Virus Infection of Human Natural Killer Cell Lines and Peripheral Blood Natural Killer Cells,” Cancer Research, Vol. 64, No. 6, 2004, pp. 2167-2174. doi:/10.1158/0008-5472.CAN-03-1562
  91. J. H. Gong, G. Maki and H. G. Klingemann, “Characterization of a Human Cell Line (NK-92) with Phenotypical and Functional Characteristics of Activated Natural Killer Cells,” Leukemia, Vol. 8, No. 4, 1994, pp. 652-658.
  92. Y. K. Tam, G. Maki, B. Miyagawa, B. Hennemann, T. Tonn and H. G. Klingemann, “Characterization of Genetically Altered, Interleukin 2-Independent Natural Killer Cell Lines Suitable for Adoptive Cellular Immunotherapy,” Human Gene Therapy, Vol. 10, No. 8, 1999, pp. 1359-1373. doi:/10.1089/10430349950018030
  93. J. W. Bruning, M. J. Kardol, R. Arentzen, A. Naipal and J. J. van der Poel, “Carboxyfluorescein Fluorochromasis Assays for Cell-Mediated Lympholysis (CML) and Antibody-Dependent Cellular Cytotoxicity (ADCC): A Non- radioactive Technique,” Transplantation Proceedings, Vol. 11, No. 4, 1979, pp. 1961-1963.
  94. H. Arase, T. Saito, J. H. Phillips and L. L. Lanier, “Cutting Edge: The Mouse NK Cell-Associated Antigen Recognized by DX5 Monoclonal Antibody Is CD49b (Alpha 2 Integrin, Very Late Antigen-2),” The Journal of Immunology, Vol. 167, No. 3, 2001, pp. 1141-1144.