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Anti-tumor Immunity Induced by Tumor Cells Expressing a Membrane-bound Form of IL-2 and SDF-1  

Choi, Jin-Wha (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
Lim, Ho-Yong (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
Chang, Mi-Ra (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
Cheon, Ji-Yeon (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
Kim, Young-Sang (Department of Biochemistry, College of Natural Sciences, Chungnam National University)
Publication Information
Animal cells and systems / v.12, no.4, 2008 , pp. 193-201 More about this Journal
Abstract
The eventual goal of tumor immunotherapy is to develop a vaccine inducing a specific anti-tumor immunity. Cytokine gene therapy is an effective way at least in animal models, but limited efficacy and various side effects obstruct clinical applications. In this study, we developed a tumor vaccine expressing a membrane-bound form of IL-2(mbIL-2) and SDF-1 in B16F10 melanoma cells. The tumor clones expressing mbIL-2 showed reduced tumorigenicity, and additional expression of SDF-1 to mbIL-2 expressing tumor cells caused more severe reduction in tumorigenicity. However, expression of the SDF-1 alone did not affect on the tumorigenicity, probably because of limited production of SDF-1 in the SDF-1 transfected clones. When the mice once rejected mbIL-2/SDF-1 expressing tumor clone were re-challenged with wild type B16F10 tumor cells, all of the mice survived. This result suggests that mbIL-2/SDF-1 tumor clone is effective in inducing systemic anti-tumor immunity against wild type B16 melanoma. Furthermore, culture supernatant of tumor clones expressing SDF-1 induced lymphocyte migration in vitro. These results, all together, suggest that expression of mbIL-2 and SDF-1 in tumor cells enhances anti-tumor immune responses through different roles; the secreted SDF-1 may function as a chemoattractant to recruit immune cells to tumor vaccine injection site, and the mbIL-2 on tumor cells may provide costimulatory signal for CTL activation in physical contacts.
Keywords
membrane-bound form of IL-2; SDF-1; tumorigenicity; systemic anti-tumor immunity;
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1 Armstrong CA, Botella R, Galloway TH, Murray N, Kramp JM, Song IS, and Ansel JC (1996) Antitumor effects of granulocyte-macrophage colony-stimulating factor production by melanoma cells. Cancer Res 56: 2191-2198
2 Campbell JJ and Butcher EC (2000) Chemokines in tissuespecific and microenvironment-specific lymphocyte homing. Curr Opin Immunol 12: 336-341   DOI   ScienceOn
3 Chang MR, Lee WH, Choi JW, Park SO, Paik SG, and Kim YS (2005) Antitumor immunity induced by tumor cells engineered to express a membrane-bound form of IL-2. Exp Mol Med 37: 240-249   DOI   ScienceOn
4 Fearon ER, Pardoll DM, Itaya T, Golumbek P, Levitsky HI, Simons JW, Karasuyama H, Vogelstein B, and Frost P (1990) Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell 60: 397-403   DOI   ScienceOn
5 Jackaman C, Bundell CS, Kinnear BF, Smith AM, Filion P, van Hagen D, Robinson BW, and Nelson DJ (2003) IL-2 intratumoral immunotherapy enhances CD8+ T cells that mediate destruction of tumor cells and tumor-associated vasculature: a novel mechanism for IL-2. J Immunol 171: 5051-5063   DOI
6 Kumar A, Humphreys TD, Kremer KN, Bramati PS, Bradfield L, Edgar CE, and Hedin KE (2006) CXCR4 physically associates with the T cell receptor to signal in T cells. Immunity 25: 213-224   DOI   ScienceOn
7 Kundig TM, Bachmann MF, DiPaolo C, Simard JJ, Battegay M, Lother H, Gessner A, Kuhlcke K, Ohashi PS, Hengartner H et al. (1995) Fibroblasts as efficient antigen-presenting cells in lymphoid organs. Science 268: 1343-1347   DOI
8 Mohle R, Bautz F, Denzlinger C, and Kanz L (2001) Transendothelial migration of hematopoietic progenitor cells. Role of chemotactic factors. Ann N Y Acad Sci 938: 26-34; discussion 34-25
9 Nomura T, Hasegawa H, Kohno M, Sasaki M, and Fujita S (2001) Enhancement of anti-tumor immunity by tumor cells transfected with the secondary lymphoid tissue chemokine EBI-1-ligand chemokine and stromal cell-derived factor- 1alpha chemokine genes. Int J Cancer 91: 597-606   DOI   ScienceOn
10 Sonn CH, Hee Ryung Yoon, In Ock Seong, Mi-Ra Chang, Yong Chan Kim, Han-Chul Kang, Seok-Cheol Suh, and Young Sang Kim (2006) MethA Fibrosarcoma Cells Expressing Membrane-Bound Forms of IL-2 Enhance Antitumor Immunity. J Microbiol Biotech 16: 1919-1927   과학기술학회마을
11 Tepper RI, Pattengale PK, and Leder P (1989) Murine interleukin-4 displays potent anti-tumor activity in vivo. Cell 57: 503-512   DOI   ScienceOn
12 Vianello F, Papeta N, Chen T, Kraft P, White N, Hart WK, Kircher MF, Swart E, Rhee S, Palu G et al. (2006) Murine B16 melanomas expressing high levels of the chemokine stromalderived factor-1/CXCL12 induce tumor-specific T cell chemorepulsion and escape from immune control. J Immunol 176: 2902-2914   DOI
13 Yei S, Bartholomew RM, Pezzoli P, Gutierrez A, Gouveia E, Bassett D, Soo Hoo W, and Carlo DJ (2002) Novel membrane-bound GM-CSF vaccines for the treatment of cancer: generation and evaluation of mbGM-CSF mouse B16F10 melanoma cell vaccine. Gene Ther 9: 1302-1311   DOI   ScienceOn
14 Allione A, Consalvo M, Nanni P, Lollini PL, Cavallo F. Giovarelli M, Forni M, Gulino A, Colombo MP, Dellabona P et al. (1994) Immunizing and curative potential of replicating and nonreplicating murine mammary adenocarcinoma cells engineered with interleukin (IL)-2, IL-4, IL-6, IL-7, IL-10, tumor necrosis factor alpha, granulocyte-macrophage colonystimulating factor, and gamma-interferon gene or admixed with conventional adjuvants. Cancer Res 54: 6022-6026
15 Kim YS, Sonn CH, Paik SG, and Bothwell AL (2000) Tumor cells expressing membrane-bound form of IL-4 induce antitumor immunity. Gene Ther 7: 837-843   DOI   ScienceOn
16 Kriegler M, Perez C, DeFay K, Albert I, and Lu SD (1988) A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. Cell 53: 45-53   DOI   ScienceOn
17 Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, Abrams J, Sznol M, Parkinson D, Hawkins M et al. (1999) High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 17: 2105-2116   DOI
18 Dilloo D, Bacon K, Holden W, Zhong W, Burdach S, Zlotnik A, and Brenner M (1996) Combined chemokine and cytokine gene transfer enhances antitumor immunity. Nat Med 2: 1090-1095   DOI   ScienceOn
19 Huang AY, Golumbek P, Ahmadzadeh M, Jaffee E, Pardoll D, and Levitsky H (1994) Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science 264: 961-965   DOI
20 Nanki T and Lipsky PE (2000) Cutting edge: stromal cell-derived factor-1 is a costimulator for CD4+ T cell activation. J Immunol 164: 5010-5014   DOI
21 murine TNF alpha. Gene Ther 4: 1181-1188. Mizoguchi H, O'Shea JJ, Longo DL, Loeffler CM, McVicar DW, and Ochoa AC (1992) Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. Science 258: 1795-1798   DOI
22 Dunussi-Joannopoulos K, Zuberek K, Runyon K, Hawley RG, Wong A, Erickson J, Herrmann S, and Leonard JP (2002) Efficacious immunomodulatory activity of the chemokine stromal cell-derived factor 1 (SDF-1): local secretion of SDF- 1 at the tumor site serves as T-cell chemoattractant and mediates T-cell-dependent antitumor responses. Blood 100: 1551-1558
23 Hillman GG, Slos P, Wang Y, Wright JL, Layer A, De Meyer M, Yudelev M, Che M, and Forman JD (2004) Tumor irradiation followed by intratumoral cytokine gene therapy for murine renal adenocarcinoma. Cancer Gene Ther 11: 61-72   DOI   ScienceOn
24 Tepper RI and Mule JJ (1994) Experimental and clinical studies of cytokine gene-modified tumor cells. Hum Gene Ther 5: 153-164   DOI   ScienceOn
25 Zier K, Gansbacher B, and Salvadori S (1996) Preventing abnormalities in signal transduction of T cells in cancer: the promise of cytokine gene therapy. Immunol Today 17: 39-45   DOI   ScienceOn
26 Nizard P, Gross DA, Babon A, Chenal A, Beaumelle B, Kosmatopoulos K, and Gillet D (2003) Anchoring cytokines to tumor cells for the preparation of anticancer vaccines without gene transfection in mice. J Immunother 26: 63-71   DOI   ScienceOn
27 Salvadori S, Gansbacher B, Pizzimenti AM, and Zier KS (1994) Abnormal signal transduction by T cells of mice with parental tumors is not seen in mice bearing IL-2-secreting tumors. J Immunol 153: 5176-5182
28 Leonard JP, Sherman ML, Fisher GL, Buchanan LJ, Larsen G, Atkins MB, Sosman JA, Dutcher JP, Vogelzang NJ, and Ryan JL (1997) Effects of single-dose interleukin-12 exposure on interleukin-12-associated toxicity and interferon-gamma production. Blood 90: 2541-2548
29 Chen K, Braun S, Lyman S, Fan Y, Traycoff CM, Wiebke EA, Gaddy J, Sledge G, Broxmeyer HE, and Cornetta K (1997) Antitumor activity and immunotherapeutic properties of Flt3- ligand in a murine breast cancer model. Cancer Res 57: 3511-3516
30 Cimino AM, Palaniswami P, Kim AC, and Selvaraj P (2004) Cancer vaccine development: protein transfer of membraneanchored cytokines and immunostimulatory molecules. Immunol Res 29: 231-240   DOI
31 Assenmacher M, Scheffold A, Schmitz J, Segura Checa JA, Miltenyi S, and Radbruch A (1996) Specific expression of surface interferon-gamma on interferon-gamma producing T cells from mouse and man. Eur J Immunol 26: 263-267   DOI   ScienceOn
32 el-Shami KM, Tzehoval E, Vadai E, Feldman M, and Eisenbach L (1999) Induction of antitumor immunity with modified autologous cells expressing membrane-bound murine cytokines. J Interferon Cytokine Res 19: 1391-1401   DOI   ScienceOn
33 Soo Hoo W, Lundeen KA, Kohrumel JR, Pham NL, Brostoff SW, Bartholomew RM, and Carlo DJ (1999) Tumor cell surface expression of granulocyte-macrophage colony-stimulating factor elicits antitumor immunity and protects from tumor challenge in the P815 mouse mastocytoma tumor model. J Immunol 162: 7343-7349
34 Baskar S, Nabavi N, Glimcher LH, and Ostrand-Rosenberg S (1993) Tumor cells expressing major histocompatibility complex class II and B7 activation molecules stimulate potent tumor-specific immunity. J Immunother 14: 209-215   DOI
35 Peled A, Petit I, Kollet O, Magid M, Ponomaryov T, Byk T, Nagler A, Ben-Hur H, Many A, Shultz L et al. (1999) Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 283: 845-848   DOI
36 Shi M, Hao S, Su L, Zhang X, Yuan J, Guo X, Zheng C, and Xiang J (2005) Vaccine of engineered tumor cells secreting stromal cell-derived factor-1 induces T-cell dependent antitumor responses. Cancer Biother Radiopharm 20: 401-409   DOI   ScienceOn
37 Nanki T, Hayashida K, El-Gabalawy HS, Suson S, Shi K, Girschick HJ, Yavuz S, and Lipsky PE (2000) Stromal cellderived factor-1-CXC chemokine receptor 4 interactions play a central role in CD4+ T cell accumulation in rheumatoid arthritis synovium. J Immunol 165: 6590-6598   DOI
38 Colombo MP, Modesti A, Parmiani G, and Forni G (1992) Local cytokine availability elicits tumor rejection and systemic immunity through granulocyte-T-lymphocyte cross-talk. Cancer Res 52: 4853-4857
39 Rivoltini L, Gambacorti-Passerini C, Squadrelli-Saraceno M, Grosso MI, Cantu G, Molinari R, Orazi A, and Parmiani G (1990) In vivo interleukin 2-induced activation of lymphokine-activated killer cells and tumor cytotoxic T-cells in cervical lymph nodes of patients with head and neck tumors. Cancer Res 50: 5551-5557
40 Zhang T, Somasundaram R, Berencsi K, Caputo L, Gimotty P, Rani P, Guerry D, Swoboda R, and Herlyn D (2006) Migration of cytotoxic T lymphocytes toward melanoma cells in three-dimensional organotypic culture is dependent on CCL2 and CCR4. Eur J Immunol 36: 457-467   DOI   ScienceOn
41 Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, Jackson V, Hamada H, Pardoll D, and Mulligan RC (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci U S A 90: 3539-3543
42 Kimura K, Nishimura H, Hirose K, Matsuguchi T, Nimura Y, and Yoshikai Y (1999) Immunogene therapy of murine fibrosarcoma using IL-15 gene with high translation efficiency. Eur J Immunol 29: 1532-1542   DOI   ScienceOn
43 Townsend SE and Allison JP (1993) Tumor rejection after direct costimulation of CD8+ T cells by B7-transfected melanoma cells. Science 259: 368-370   DOI
44 Kurt-Jones EA, Fiers W, and Pober JS (1987) Membrane interleukin 1 induction on human endothelial cells and dermal fibroblasts. J Immunol 139: 2317-2324
45 Lu X, Kallinteris NL, Li J, Wu S, Li Y, Jiang Z, Hillman GG, Gulfo JV, Humphreys RE, and Xu M (2003) Tumor immunotherapy by converting tumor cells to MHC class IIpositive, Ii protein-negative phenotype. Cancer Immunol Immunother 52: 592-598   DOI   ScienceOn
46 Lollini PL and Forni G (2003) Cancer immunoprevention: tracking down persistent tumor antigens. Trends Immunol 24: 62-66   DOI   ScienceOn
47 Marr RA, Addison CL, Snider D, Muller WJ, Gauldie J, and Graham FL (1997) Tumour immunotherapy using an adenoviral vector expressing a membrane-bound mutant of murine TNF alpha. Gene Ther 4: 1181-1188   DOI   ScienceOn
48 Nanni P, Forni G, and Lollini PL (1999) Cytokine gene therapy: hopes and pitfalls. Ann Oncol 10: 261-266
49 Tjuvajev J, Gansbacher B, Desai R, Beattie B, Kaplitt M, Matei C, Koutcher J, Gilboa E, and Blasberg R (1995) RG-2 glioma growth attenuation and severe brain edema caused by local production of interleukin-2 and interferon-gamma. Cancer Res 55: 1902-1910
50 Emoto M, Mittrucker HW, Schmits R, Mak TW, and Kaufmann SH (1999) Critical role of leukocyte function-associated antigen-1 in liver accumulation of CD4+NKT cells. J Immunol 162: 5094-5098
51 Luo L, Chapoval AI, Flies DB, Zhu G, Hirano F, Wang S, Lau JS, Dong H, Tamada K, Flies AS et al. (2004) B7-H3 enhances tumor immunity in vivo by costimulating rapid clonal expansion of antigen-specific CD8+ cytolytic T cells. J Immunol 173: 5445-5450   DOI
52 Gabrilovich DI, Ciernik IF, and Carbone DP (1996) Dendritic cells in antitumor immune responses. I. Defective antigen presentation in tumor-bearing hosts. Cell Immunol 170: 101-110   DOI   ScienceOn
53 Gansbacher B, Zier K, Daniels B, Cronin K, Bannerji R, and Gilboa E (1990) Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity. J Exp Med 172: 1217-1224   DOI   ScienceOn
54 Browning JL, Ngam-ek A, Lawton P, DeMarinis J, Tizard R, Chow EP, Hession C, O'Brine-Greco B, Foley SF, and Ware CF (1993) Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface. Cell 72: 847-856   DOI   ScienceOn
55 Blankenstein T, Rowley DA, and Schreiber H (1991) Cytokines and cancer: experimental systems. Curr Opin Immunol 3: 694-698   DOI   ScienceOn