Inhibition of Human Pancreatic Tumor Growth by Cytokine-Induced Killer Cells in Nude Mouse Xenograft Model
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Pancreatic cancer is the fourth commonest cause of cancer-related deaths in the world. However, no adequate therapy for pancreatic cancer has yet been found. In this study,the antitumor activity of cytokine-induced killer (CIK) cells against the human pancreatic cancer was evaluated in vitro and in vivo. Human peripheral blood mononuclear cells were cultured with IL-2-containing medium in anti-CD3 for 14days. The resulting populations of CIK cells comprised 94%CD3^＋, 4% CD3^−CD56^＋, 41% CD3^＋CD56^＋, 11% CD4^＋,and 73% CD8^+. This heterogeneous cell population was called cytokine-induced killer (CIK) cells. At an effector-target cell ratio of 100：1, CIK cells destroyed 51% of AsPC-1human pancreatic cancer cells, as measured by the ^(51)Cr-release assay. In addition, CIK cells at doses of 3 and 10 million cells per mouse inhibited 42% and 70% of AsPC-1 tumor growth in nude mouse xenograft assays, respectively. This study suggests that CIK cells may be used as an adoptive immunotherapy for pancreatic cancer patients.
Abstract
Pancreatic cancer is the fourth commonest cause of cancer-related deaths in the world. However, no adequate therapy for pancreatic cancer has yet been found. In this study,the antitumor activity of cytokine-induced killer (CIK) cells against the human pancreatic cancer was evaluated in vitro and in vivo. Human peripheral blood mononuclear cells were cultured with IL-2-containing medium in anti-CD3 for 14days. The resulting populations of CIK cells comprised 94%CD3^＋, 4% CD3^−CD56^＋, 41% CD3^＋CD56^＋, 11% CD4^＋,and 73% CD8^+. This heterogeneous cell population was called cytokine-induced killer (CIK) cells. At an effector-target cell ratio of 100：1, CIK cells destroyed 51% of AsPC-1human pancreatic cancer cells, as measured by the ^(51)Cr-release assay. In addition, CIK cells at doses of 3 and 10 million cells per mouse inhibited 42% and 70% of AsPC-1 tumor growth in nude mouse xenograft assays, respectively. This study suggests that CIK cells may be used as an adoptive immunotherapy for pancreatic cancer patients.
참고문헌 (30)
- Hariharan, D., "Analysis of mortality rates for pancreatic cancer across the world", HPB (Oxford), 10, pp.58~62 (2008)
- Jemal, A., "Cancer statistics,2010", CA Cancer J. Clin, 60, pp.277~300 (2010)
- Koido, S., "Current immunotherapeutic approaches in pancreatic cancer", Clin. Dev. Immunol, pp.267539~ (2011)
- Burris, H. A., "Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial", J. Clin. Oncol, 15, pp.2403~2413 (1997)
- Weng, D., "Induction of cytotoxic T lymphocytes against ovarian cancer-initiating cells", Int. J. Cancer, 129, pp.1990~2001 (2011)
- Neoptolemos, J. P, "A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer", N. Engl. J. Med, 350, pp.1200~1210 (2004)
- Hwan Mook Kim, "Antitumor Activity of Cytokine-induced Killer Cells in Nude Mouse Xenograft Model", Archives of Pharmacal Research, 32(5), pp.781~787 (2009), 대한약학회
- Franceschetti, M., "Cytokine-induced killer cells are terminally differentiated activated CD8 cytotoxic T-EMRA lymphocytes", Exp. Hematol, 37, pp.616~628 (2009)
- Schmidt-Wolf, I. G, "Use of a SCID mouse", human lymphoma model to evaluate cytokine-induced killer cells with potent antitumor cell activity, 1991, pp.174, 139~149
- Schmidt-Wolf, I. G., "Phenotypic characterization and identification of effector cells involved in tumor cell recognition of cytokine-induced killer cells", Exp. Hematol, 21, pp.1673~1679 (1993)
- Kim, H. M, "Antitumor activity of cytokine- induced killer cells against human lung cancer", Int. Immunopharmacol, 7, pp.1802~1807 (2007)
- Kim, H. M, "Anti-tumor activity of ex vivo expanded cytokine-induced killer cells against human hepatocellular carcinoma", Int. Immunopharmacol, 7, pp.1793~1801 (2007)
- Takayama, T., "Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial", Lancet, 356, pp.802~807 (2000)
- Kornacker, M., "Cytokine-induced killer cells against autologous CLL: direct cytotoxic effects and induction of immune accessory molecules by interferon-gamma", Int. J. Cancer, 119, pp.1377~1382 (2006)
- Yang, X. J., "Antitumor effects of cocultured dendritic cells and cytokine-induced killer cells on lung cancer in vitro and in vivo", Ai Zheng, 25, pp.1329~1333 (2006)
- Hwan Mook Kim, "Inhibition of Human Ovarian Tumor Growth by Cytokine-induced Killer Cells", Archives of Pharmacal Research, 30(11), pp.1464~1470 (2007), 대한약학회
- Wang, W, "Recognition of breast cancer cells by CD8+ cytotoxic T-cell clones specific for NY-BR-1", Cancer Res, 66, pp.6826~6833 (2006)
- Sun, S., "Studies on inducing apoptosis effects and mechanism of CIK cells for MGC-803 gastric cancer cell lines", Cancer Biother. Radiopharm, 20, pp.173~180 (2005)
- Verneris, M. R., "Role of NKG2D signaling in the cytotoxicity of activated and expanded CD8+ T cells", Blood, 103, pp.3065~3072 (2004)
- 한상배, "The inhibitory effect of polysaccharide isolated from Phellinus linteus on tumor growth and metastasis", INTERNATIONAL IMMUNOPHARMACOLOGY, 41, pp.157~164, ELSEVIER SCIENCE BV
- Kim, J. Y, "Angelan isolated from Angelica gigas Nakai induces dendritic cell maturation through toll-like receptor 4", Int. Immunopharmacol, 7, pp.78~87 (2007)
- Kalinski, P, "Helper roles of NK and CD8+ T cells in the induction of tumor immunity. Polarized dendritic cells as cancer vaccines", Immunol. Res, 36, pp.137~146 (2006)
- Takashima, K., "Tracking of green fluorescent protein (GFP)-labeled LAK cells in mice carrying B16 melanoma metastases", Anticancer Res, 26, pp.3327~3332 (2006)
- Raja Gabaglia, C., "Attenuation of the glucocorticoid response during Ad5IL-12 adenovirus vector treatment enhances natural killer cell-mediated killing of MHC class I-negative LNCaP prostate tumors", Cancer Res, 67, pp.2290~2297 (2007)
- Thorne, S. H, "Synergistic antitumor effects of immune cell-viral biotherapy", Science, 311, pp.1780~1784 (2006)
- Grabert, R. C, "Human T cells armed with Her2", neu bispecific antibodies divide, are cytotoxic, and secrete cytokines with repeated stimulation, 2006, pp.12, 569~576
- Alvarnas, J. C, "Expansion of cytotoxic CD3+ CD56+ cells from periph eral blood progenitor cells of patients undergoing autologoushematopoietic cell transplantation", Biol. Blood Marrow Tran, 7, pp.216~222 (2001)
- Lu, P. H., "A novel population of expanded human CD3＋CD56＋ cells derived from T cells with potent in vivo antitumor activity in mice with severe combined immunodeficiency", J. Immunol, 153, pp.1687~1696 (1994)
- Pievani, A, "Dual-functional capability of CD3+CD56+ CIK cells, a T-cell subset that acquires NK function and retains TCR-mediated specific cytotoxicity", Blood, 118, pp.3301~3310 (2011)
- Kim, H. M, "Inhibition of human cervical carcinoma growth by cytokine- induced killer cells in nude mouse xenograft model", Int. Immunopharmacol, 9, pp.375~380 (2009)