Anti-cancer Effect of Hematopoietic Stem Cell-derived Allogeneic-DC Vaccine in Melanoma Metastasis Model

마우스 동종 줄기세포 유래 수지상 세포를 이용한 백신의 흑색종 폐암 전이 모델에서의 항암 효과 및 기전 연구

  • Kim, Myoung-Joo (The Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Shon, Hye-Jin (The Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Baek, So-Young (The Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Kang-Eun (The Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Young-Joon (Medipost Biomedical Research Institute) ;
  • Lee, Hyun-Ah (The Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 김명주 (성균관대학교 의과대학 삼성서울병원 암센터) ;
  • 손혜진 (성균관대학교 의과대학 삼성서울병원 암센터) ;
  • 백소영 (성균관대학교 의과대학 삼성서울병원 암센터) ;
  • 이강은 (성균관대학교 의과대학 삼성서울병원 암센터) ;
  • 이영준 (㈜메디포스트 중앙연구소) ;
  • 이현아 (성균관대학교 의과대학 삼성서울병원 암센터)
  • Published : 2006.09.30

Abstract

Background: Dendritic cell (DC)-based cancer immunotherapy is studied for several years. However, it is mainly derived from autologous PBMC or leukapheresis from patient, which has limitations about yield and ability of DC production according to individual status. In order to solve these problems, inquiries about allogeneic DCs are performed but there are no preclinical trial answers for effect or toxicity of allogeneic DC to use for clinical trial. In this study, we compared the anti-tumor effect of allogeneic and autologous DCs from mouse bone marrow stem cells in mouse metastatic melanoma model. Methods: B16F10 melanoma cells ($5{\times}10^4$/mouse) were injected intravenously into the C57BL/6 mouse. Therapeutic DCs were differentiated from autologous (C57BL/6: CDC) or allogeneic (B6C3F1: BDC) bone marrow stem cells with GM-CSF, SCF and IL-4 for 13days and pulsed with B16F10 tumor cell lysate (Blys) for 18hrs. DC intra-peritoneal injections began on the 8th day after the tumor cell injection by twice with one week interval. Results: Anti-tumor response was observed by DC treatment without any toxicity especially in allogeneic DC treated mice (tumor burden score: $2.667{\pm}0.184,\;2.500{\pm}0.463,\;2.000{\pm}0.286,\;1.500{\pm}0.286,\;1.667 {\pm}0.297$ for saline, CDC/unpulsed-DC: U-DC, CDC/Blys-DC, BDC/U-DC and BDC/Blys-DC, respectively). IFN-${\gamma}$ secretion was significantly increased in allogeneic DC group stimulated with B16F10 cell lysate ($2,643.3{\pm}5,89.7,\;8,561.5{\pm}2,204.9.\;6,901.2{\pm}141.1pg/1{\times}10^6$ cells for saline, BDC/U-DC and BDC/Blys-DC, respectively) with increased NK cell activity. Conclusion: Conclusively, promising data was obtained that allogeneic DC can be used for DC-based cancer immunotherapy.

Keywords

References

  1. Hsu FJ, Benike C, Fagnoni F, Liles TM, Czerwinski D, Taicli B: Vaccination of patients with B-cell lymphoma using autol ogous antigen-pulsed dendritic cells. Nat Med 2;52-58, 1996 https://doi.org/10.1038/nm0196-52
  2. Lee YJ, Kim MJ, IN SH, Choi OM, Baek S, Kwon YD, Lee H: Effect of dendritic cell based cancer vaccine using allogeneic tumor cell lysate in melanoma pulmonary metastasis model. Immune Network 5;163-171, 2005 https://doi.org/10.4110/in.2005.5.3.163
  3. Nencioni A, Brossart P: Cellular immunotherapy with dendritic cells in cancer: current status. Stem Cells 22;501-513, 2004 https://doi.org/10.1634/stemcells.22-4-501
  4. Curti A, Isioiri A, Ferri E, Terragna C, Neyroz P, Cellini C, Ratta M, Baccarani M, Lemoli Rvl: Generation of dendritic cells from positively selected CD1$ 4^{+}$ monocytes for antitumor immunotherapy. Leukemia & Lymphoma 45;1419-1428, 2004 https://doi.org/10.1080/10428190310001653682
  5. Figdor CG, De Vires IJM, Lesterhuis WJ, Melief CJM: Dendritic cell immunotherapy: mapping the way. Leuk Lymphoma 10;475-480, 2004
  6. Lee H, Choi KM, Baek S, Lee HG, Jung CW: Dendritic cell based cancer immunotherapy: in vivo study with mouse renal cell carcinoma model. Immune Network 4;44-52, 2004 https://doi.org/10.4110/in.2004.4.1.44
  7. Dietz AB, Padley DJ, Butler GW, Maas ML, Greiner CW, Gastineau DA, Pavolovic SV: Clinical-grade manufacturing of DC from CD1$ 4^{+}$ precursors: experience from phase I clinical trials in CML and malignant melanoma. Cytotherapy 6;563-570, 2004 https://doi.org/10.1080/14653240410005357-1
  8. Schuler-Thurner B, Schultz ES, Berger TG, Weinlich G, Ebner S, Toerl P, Bender A, Feuerstein B, Fritsch PO, Romani N, Schuler G: Rapid induction of tumor-specific type 1 T helper cells in metastatic melanoma patients by vaccination with mature, cryopreserved, peptide-loaded monocyte-derived dendritic cells. J Exp Med 195;1279-1288, 2002 https://doi.org/10.1084/jem.20012100
  9. Holtl L, Zeller-Rieser C, Gander H, Papesh C, Ramoner R, Bartsch G, Rogatsch H, Barsoum AL Coggin JH Jr, Thurnher M: Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells. Clin Cancer Res 8;3369-3376, 2002
  10. O'Rourke MGE, Johnson M, Lanagan C, See J, Yang J, Bell JR, Slater GJ, Kerr BM, Crowe B, Purdie DM, Elliott SL, Ellem KAO, Schmidt CW: Durable complete clinical responses in a phase I/II trial using an autologous melanoma cell/ dendritic cell vaccine. Cancer Immunol Immunother 52;387-395, 2003
  11. Iwashita Y, Tahara K, Goto S, Sasaki A, Kai S, Seike M, Cehn CL, Kawano K, Kitano S: A phase I study of autologous dendritic cell-based immunotherapy for patients with unresectable primary liver cancer. Cancer Immunol Immunother 52;155-161, 2003
  12. Ward KA, Stewart LA, Schwarer AP: CD34$^{+}$ -derived CD11c $^{+++}$ BDCA-1 $^{++}$ CD123$^{++}$ DC: expansion of a phenotypically undescribed myeloid DC1 population for use in adoptive immunotherapy. Cytotherapy 8;130-140, 2006 https://doi.org/10.1080/14653240600620689
  13. Li-Cheng Xu RL, Tang Y, Ogburn PL Malinowski K, Malhjewicz S, Santiago-Schwarz F, Fan Q: Implication of delayed TNF-alpha exposure on dendritic cell maturation and expansion from cryopreserved cord blood CD3$4^{+}$ hematopoietic progenitors. J Immunol Methods 293;169-182, 2004 https://doi.org/10.1016/j.jim.2004.08.001
  14. Encabo A, Solves P, Mateu E, Sepulveda P, Carbonell-Uberos F, Minana MD: Selective generation of different dendritic cell precursors from CD3$ 4^{+}$ cells by intcrlcukin-6 and interleukin-3. Stem Cells 22;725-740, 2004 https://doi.org/10.1634/stemcells.22-5-725
  15. Dilioglou S, Cruse JM, Lewis RE: Function of CD80 and CD86 on monocyte- and stem cell-derived dendritic cells. Exp Mol Pathol 75;217-227, 2003 https://doi.org/10.1016/S0014-4800(03)00072-8
  16. Guanghua G, Suzuan C, Juan Z, Lili I., Jing Y, Hongmei D, Hong X, Zhongjing S, Libiao W: Antitumor activity of a fusion of esophageal carcinoma cells with dendritic cells derived from cord blood. Vaccine 23;5225-5230, 2005 https://doi.org/10.1016/j.vaccine.2005.07.080
  17. Guardino AE, Rajapaksa R, Ong KH, Sheehan K, Levy R: Production of myeloid dendritic cells (DC) pulsed with tumorspecific idiotype protein for vaccination of patients with multiple myeloma. Cytotherapy 8;277-289, 2006 https://doi.org/10.1080/14653240600735701
  18. Hus I, Rolinski J, Tabarkiewicz J, Wojas K, Bojarska-Junak A, Greiner J, Giannopoulos K, Dmoszynska A, Schmitt M: Allogeneic dendritic cells pulsed with tumor lysates or apoptotic bodies as immunotherapy for patients with early-stage B-cell chronic lymphocytic leukemia. Leukemia 19;1621-1627, 2005 https://doi.org/10.1038/sj.leu.2403860
  19. Marten A, Renoth S, Heinicke T, Alebers P, Pauli A, Mey U, Caspari R, Flieger D, Hanfland P, Ruecker A V, EisHubinger AM, Muller S, Schwaner I, Lohmann U, Heymann G, Sauerbruch T, Scgmidt-Wolf IGH: Allogeneic dendritic cells fused with tumor cells: preclinical results and outcome of a clinical phase I/ll trial in patients with metastatic renal cell carcinoma. Hum Gene Ther 14;483-494, 2003 https://doi.org/10.1089/104303403321467243
  20. Wagner JE, Barker JN, Defor TE, Baker KC, Blazer BR, Eide C, Goldman A, Kersey J, Krivit W, MacMillan ML, Orchard PJ, Peters C, Weisdorf DJ, Ramsay NKC, Davies SM: Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival. Blood 100;1611-1618, 2002
  21. Yoon HL Singh K, Ratner S, Reiners JJ: Phorbol ester effects on splenic lymphocyte composition and cytotoxic T cell activities of SSIN mice: a strain deficient in CD$8^{+}$ T cells. Carcinogenesis 17;2617-2624, 1996 https://doi.org/10.1093/carcin/17.12.2617
  22. Pulendran B, Maraskovsky E, Banchereau J, Malaliszewski C: Modulating the immune response with dendritic cells and their growth factors. Trends Immunol 22;41-47, 2001 https://doi.org/10.1016/S1471-4906(00)01794-4
  23. Parmiani G, Castelli C, Rivoltini L, Casati C, Tully GA, Novellino L, Patuzzo A, Tosi D, Santinami M: Immnotherapy of melanoma. Sernin Cancer Biol 13;391-400, 2003 https://doi.org/10.1016/j.semcancer.2003.09.001
  24. Lee SJ, Kim MJ, In SH, Baek S, Lee H: Immunocell therapy for lung cancer: dendritic cell based adjuvant therapy in mouse lung cancer model. Immune Network 5;36-44, 2005 https://doi.org/10.4110/in.2005.5.1.36
  25. Moser M, Murphy KM: Dendritic cell regulation of T$T_{H}1-T_{H}$2 development. Nature Immunol 1;199-204, 2000 https://doi.org/10.1038/79734
  26. Martin P, Martinez del Hoyo G, Anjuere F, Ruiz SR, Arias CF, Marin AR, Ardavin C: Concept of lymphoid versus myeloid dendritic cell lineages revisited: both CD8$alpha^{-}$ and CD8 $ alpha^{+}$ dendritic cells are generated from CD lymphoidcommitted precursors. Blood 96;2511-2519, 2000
  27. Mohty M, Olive D, Gaugler B: Leukemic dendritic cells: Potential for therapy and insights towards immune escape by leukemic blasts. Leukemia 16;2197-2204, 2002 https://doi.org/10.1038/sj.leu.2402710
  28. Ratzinger G, Baggers J, de Cos MA, Yuan J, Dao T, Reagan JL, Munz C, Heller G, Young JW: Mature human langerhans cells derived from CD3$4^{+}$ hematopoietic progenitors stimulate greater cytolytic T lymphocyte activity in the absence of bioactivc IL-12p70, by either single peptide presentation or cross-priming, than do dermal-interstitial or monocytederived dendritic cells. J Immunol 173;2780-2791, 2004 https://doi.org/10.4049/jimmunol.173.4.2780
  29. O'Garra A, Vieira P: Regulatory T cells and mechanisms of immune system control. Nat Med 10;801-805, 2004 https://doi.org/10.1038/nm0804-801
  30. Van den Broeke LT, Daschbach E, Thomas EK, Andringa G, Berzofsky JA: Dendritic cell-induced activation of adaptive and innate antitumor immunity. J Immunol 171;5842-5852, 2003 https://doi.org/10.4049/jimmunol.171.11.5842
  31. Osada T, Clay T, Hobeika A, Lyerly HK, Morse MA: NK cell activation by dendritic cell vaccine: a mechanism of action for clinical activity. Cancer Immunol Immunother 55; 1122-1131, 2006 https://doi.org/10.1007/s00262-005-0089-3
  32. Mailliard RB, Son YI, Redlinger R, Coates PT, Giermasz A, Penelope AM, Storkus WJ, Kalinski P: Dendritic cells mediate NK cell help for Th1 and CTL responses: two-signal requirement for the induction of NK cell helper function. J Immunol 171;2366-2373, 2003 https://doi.org/10.4049/jimmunol.171.5.2366
  33. Kalinski P, Giermasz A, Nakamura Y, Basse P, Storkus WJ, Kirkwood JM, Mailliard RB: Helper role of NK cells during the induction of anticancer responses by dendritic cells. Mol Immunol 42;535-539, 2005 https://doi.org/10.1016/j.molimm.2004.07.038
  34. Gerosa F, Gobbi A, Zorzi P, Burg S, Briere F, Carra G, Trinchicri G: The reciprocal interaction of NK cells with plasmacytoid or myeloid dendritic cells profoundly affects innate resistance functions. J Immunol 174;727-734, 2005 https://doi.org/10.4049/jimmunol.174.2.727