The Effectiveness of IL-12 Administration and Fusion on Tumor Antigen Sensitization Methods for Dendritic Cells Derived from Patients with Myelogenous Leukemia

골수성백혈병에서 배양한 수지상세포(Dendritic Cell)에 대한 종양항원 감작법으로 IL-12 첨가와 융합법의 효과

  • Kim, Kee Won (Department of Internal Medicine, Medical College, The Catholic University of Korea) ;
  • Park, Suk Young (Department of Internal Medicine, Medical College, The Catholic University of Korea) ;
  • Hong, Young Seon (Department of Internal Medicine, Medical College, The Catholic University of Korea)
  • 김기원 (가톨릭대학교 의과대학 내과학교실) ;
  • 박석영 (가톨릭대학교 의과대학 내과학교실) ;
  • 홍영선 (가톨릭대학교 의과대학 내과학교실)
  • Published : 2004.03.31

Abstract

Backgroud: Immunotherapy using dendritic cells (DC) loaded with tumor antigens may represent a potentially effective method for inducing antitumor immunity. We evaluated the effectiveness of DC-based antitumor immune response in various conditions. Methods: DC were cultured from peripheral blood mononuclear cells (PBMNC) in myelogenous leukemia (ML) and lysates of autologous leukemic cells are used as tumor antigen. The effectiveness of interleukin-12 (IL-12) and CD40L (CD154) on the antigen presenting function of lysates-loaded DC was analyzed by proliferation, cytokine production, and cytotoxicity tests with activated PBMNC (mainly lymphocytes). For generating antigen-loaded DC, direct fusion of DC with ML was studied. Results: Antigen loaded DC induced significantly effective antitumor immune response against autologous leukemic cells. Administration of IL-12 on the DC based antitumor immune response showed higher proliferation activity, IFN-$\gamma$ production, and cytotoxic activity of PBMNC. Also, fused cell has a potent antitumor immune response. Conclusion: We conclude that lysates-loaded DC with IL-12 may be effectively utilized as inducer of antitumor immune reaction in ML and in vivo application with DC-based antitumor immunotherapy or tumor vaccination seems to be feasible.

Acknowledgement

Supported by : 가톨릭암센터

References

  1. Herberman RB: Tumor immunology. JAMA 268;2935-2939, 1993.
  2. Van Schooten WCA, Strang G, Palathumpat V: Biological properties of dendritic cells: implications to their use in the treatment of cancer. Mol Med Today 3;254-260, 1997 https://doi.org/10.1016/S1357-4310(97)01047-2
  3. Austyn JM, Phil MA: Dendritic cells. Cur Opin in Hematol 5;3-15, 1998 https://doi.org/10.1097/00062752-199801000-00002
  4. Gilboa E, Nair SK, Lyerly HK: Immunotherapy of cancer with dendritic-cell-based vaccines. Cancer Immunol Immunother 46;82-87, 1998 https://doi.org/10.1007/s002620050465
  5. Morse MA, Lyerly HK: Immunotherapy of cancer using dendritic cells. Cytokines, Cell Mol Ther 4;35-44, 1998
  6. Romani N, Gruner S, Brang D, Kampgen E, Lenz A, Trockenbacher B, Konwalinka G, Fritsch PO, Steinman RM, Schuler G: Proliferation dendritic cell progenitors in human blood. J Exp Med 180;83-93, 1994 https://doi.org/10.1084/jem.180.1.83
  7. Mukherji B, Chakraborty NG, Yamasaki S: Induction of human antigen-specific cytolytic T cells in situ in human melanoma by immunization with synthetic peptide-pulsed dendritic cells. Nat Med 2;52-58, 1997 https://doi.org/10.1038/nm0196-52
  8. Salgaller ML, Tjoa BA, Lodge H, Kenny G, Boynton A, Murphy GP: Dendritic cell-based immunotherapy of prostate cancer. Crit Rev Immunol 18;109-119, 1998 https://doi.org/10.1615/CritRevImmunol.v18.i1-2.120
  9. Hsu FJ, Benike C, Fagnoni F, Liles TM, Czerwinski D, Taidi B, Engleman EG, Levy R: Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med 2;52-58, 1996 https://doi.org/10.1038/nm0196-52
  10. Doczkowski D, Nair SK, Snyder D, Gilboa E: Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J Exp Med 184;465-472, 1996 https://doi.org/10.1084/jem.184.2.465
  11. Gong J, Chen D, Kashiwaba M, Kufe D: Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells. Nat Med 3;558-561, 1997 https://doi.org/10.1038/nm0597-558
  12. Lespagnard L, Mettens P, Verheyden A, Tasiaux N, Thielemans K, van Meirvenne S, Geldhof A, de Baetselier P, Urbain J, Leo O, Moser M: Dendritic cells fused with mastoctoma cells elicit therapeutic antitumor immunity. Int J Cancer 76;250-258, 1998 https://doi.org/10.1002/(SICI)1097-0215(19980413)76:2<250::AID-IJC13>3.0.CO;2-G
  13. Wu S, Ma J, Che X, Liu Y, Wang H, Zhao J, Shen F, Xie T, Trojan J, Wu M, Guo Y: Treatment of hepatocellular carcinoma with the cellular tumor vaccines generated by in vitro modification of tumor cells with non gene transfer approaches. Adv Exp Med Biol 451;283-293, 1998
  14. Weidmann F, Brieger J, Jahn B, Hoelzer D, bergmann L, Mitrou PS: Lactate dehydrogenase-release assay: A reliable, nonradioactive technique for analysis of cytotoxic lymphocyte-mediated lytic activity against blasts from acute myelocytic leukemia. Ann Hematol 70;153-158, 1995 https://doi.org/10.1007/BF01682036
  15. Park SY, Kim KW: In vitro culture of dendritic cells and activation of peripheral blood nomononuclear cells in patients with chronic myelogenous leukemia. Korean J Hematol 35;50-57, 2000.
  16. Gately MK, Wolitzky AG, Quinn PM, Chizzonite R: Regulation of human cytolytic lymphocyte responses by interleukin-12. Cell Immunol 143;127-142, 1992 https://doi.org/10.1016/0008-8749(92)90011-D
  17. Terheyden P, Straten P, Brocker E, Kampgen E, Becker J:CD40-ligated dendritic cells effectively expand melanoma- specific CD8+ CTLs and CD4+ IFN-$\gamma$-producing T cells from tumor-infiltrating lymphocytes. J Immunol 164;6633-6639, 2000 https://doi.org/10.4049/jimmunol.164.12.6633
  18. Sato T, Terai M, Yasuda R, Watanabe R, Berd D, Mastrangelo M, Hasumi K: Combination of monocyte-derived dendritic cells and activated T cells which express CD40 ligand: a new approach to cancer immunotherapy. Cancer Immunol Immunother 53;53-61, 2004 https://doi.org/10.1007/s00262-003-0419-2
  19. Hoffmann TK, Meidenbauer N, Muller-Berghous J, Storkus WJ, Whiteside TL: Proinflammatory cytokines and CD40 ligand enhance cross-presentation and cross-priming capacity of human dendritic cells internalizing apoptotic cancer cells. J Immunother 24;162-171, 2001 https://doi.org/10.1097/00002371-200103000-00011
  20. Luft T, Jefford M, Luetjens P, Hochrein H, Masterman K, Maliszewski C, Shortman K, Cebon J, Maraskovsky E: Functionally distinct dendritic cell populations induced by physiologic stimuli: prostaglandin E2 regulates the migratory capacity of specific DC subsets. Blood 200;1362-1372, 2002
  21. Lentz BR: Polymer-induced membrane fusion: potential mechanism and relation to cell fusion events. Chem Phys Lipids 73;91-106, 1994 https://doi.org/10.1016/0009-3084(94)90176-7
  22. Scott-Taylor TH, Pettengell R, Clarke I, Stuhler G, La Barthe MC, Walden P, Dalgleish AG: Human tumour and dendritic cell hybrids generated by electrofusion: potential for cancer vaccines. Biochim Biophys Acta 1500;265-279, 2000 https://doi.org/10.1016/S0925-4439(99)00108-8
  23. Tsurudome M, Ito Y: Function of fusion regulatory proteins in immune cells and virus-infected cells. Crit Rev Immunol 10;167-196, 2000