Dendritic Cell Based Cancer Immunotherapy: in vivo Study with Mouse Renal Cell Carcinoma Model

수지상세포를 이용한 항암 면역 치료: 생쥐 신장암 모델을 이용한 연구

  • Lee, Hyunah (The Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Choi, Kwang-Min (The Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Baek, Soyoung (The Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Hong-Ghi (Division of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jung, Chul-Won (Division of Hematology and Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 이현아 (성균관대학교 의과대학 삼성서울병원 암센터) ;
  • 최광민 (성균관대학교 의과대학 삼성서울병원 암센터) ;
  • 백소영 (성균관대학교 의과대학 삼성서울병원 암센터) ;
  • 이홍기 (성균관대학교 의과대학 삼성서울병원 혈액종양내과) ;
  • 정철원 (성균관대학교 의과대학 삼성서울병원 혈액종양내과)
  • Published : 2004.03.31

Abstract

Background: As a potent antigen presenting cell and a powerful inducer of antigen specific immunity, dendritic cells (DCs) are being considered as a promising anti-tumor therapeutic module. The expected therapeutic effect of DCs in renal cell carcinoma was tested in the mouse model. Established late-stage tumor therapeutic (E-T) and minimal residual disease (MRD) model was considered in the in vivo experiments. Methods: Syngeneic renal cell carcinoma cells (RENCA) were inoculated either subcutaneously (E-T) or intravenously (MRD) into the Balb/c mouse. Tumor cell lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started 3 week (E-T model) or one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, the tumor growth and the systemic immunity were observed. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with RENCA cell lysate for 18 hrs. Results: Compared to the saline treated group, tumor growth (E-T model) or formation (MRD model) was suppressed in pulsed-DC treated group. RENCA specific lymphocyte proliferation was observed in the RENCA tumor-bearing mice treated with pulsed-DCs. Primary cytotoxic T cell activity against RENCA cells was increased in pulsed-DC treated group. Conclusion: The data suggest the possible anti-tumor effect of cultured DCs in established or minimal residual disease/metastasis state of renal cell carcinoma. Systemic tumor specific immunity including cytotoxic T cell activity was modulated also in pulsed-DC treated group.

Keywords

Acknowledgement

Supported by : 삼성생명과학연구소

References

  1. Steinman RM, Cohn ZA: Identificaion of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 137;1142-1162, 1973 https://doi.org/10.1084/jem.137.5.1142
  2. Steinman RM: Prospects for immunotherapy directed to the T cell receptor in human autoimmune disease. Ann N Y Acad Sci 636;147-153, 1991 https://doi.org/10.1111/j.1749-6632.1991.tb33445.x
  3. Shurin MR: Dendritic cells presenting tumor antigen. Cancer Immunol Immunother 43;158, 1996 https://doi.org/10.1007/s002620050317
  4. Banchereau J, Steinman RM: Dendritic cells and the control of immunity. Nature 392;245-252, 1998 https://doi.org/10.1038/32588
  5. Palucka K, Banchereau J: Dendritic cells: a link between innate and adaptive immunity. J Clin Immunol 19;12-25, 1999 https://doi.org/10.1023/A:1020558317162
  6. Palucka K, Banchereau J: Linking innate and adaptive immunity. Nat Med 5;868-870, 1999 https://doi.org/10.1038/11303
  7. Inaba K, Young JW, Steinman RM : Direct activation of CD8+ cytotoxic T lymphocytes by dendritic cells. J Exp Med 166;182-194, 1987 https://doi.org/10.1084/jem.166.1.182
  8. Inaba K, Metlay JP, Crowley MT, Steinman RM: Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ. J Exp Med 172;631-640, 1990 https://doi.org/10.1084/jem.172.2.631
  9. Flamand V, Sornasse T, Thielenabs K, Demanet C, Bakkus M, Bazin H, Thielemans C, Leo O, Urbain J, Moser M: Murine dendritic cells pulsed in vitro with tumor antigen induce tumor resistance in vivo. Eur J Immunol 24;605-610, 1994 https://doi.org/10.1002/eji.1830240317
  10. Celluzzi C, Mayordomo JI, Storkus WJ, Lotze MT, Falo LD:Peptide-pulsed dendritic cells induce antigen-specific, CTLmediated protective tumor immunity. J Exp Med 183;283-288, 1996 https://doi.org/10.1084/jem.183.1.283
  11. Hart DNJ: Dendritic cells: Unique leukocyte populations which control the primary immune response. Blood 90(9);3245-3287, 1997.
  12. Kurokawa T, Oelke M, Mackensen A: Induction and clonal expansion of tumor-specific cytotoxic T lymphocytes from renal cell carcinoma patients after stimulation with autologous dendritic cells loaded with tumor cells. Int J Cancer 91;749, 2001 https://doi.org/10.1002/1097-0215(200002)9999:9999<::AID-IJC1141>3.0.CO;2-X
  13. Muller L, Provenzani C, Faul C, Pawelec G: Recognition of chronic myelogeneous leukemia cells by autologous T lymphocytes primed in vitro against the patient's dendritic cells. Br J Haematol 112(3);740-748, 2001 https://doi.org/10.1046/j.1365-2141.2001.02596.x
  14. Fernandez N et.al.: Dendritic cells directly trigger NK cell functions: Cross-talk relevant in innate anti-tumor immune responses in vivo. Nature Medicine 5(4);405-410, 1999 https://doi.org/10.1038/7403
  15. Young Robert C: Metastatic renal-cell carcinoma: what causes occasional dramatic regressions? The New England Journal of Medicine 338(18);1305-1306, 1998 https://doi.org/10.1056/NEJM199804303381811
  16. Annual Report of the Central Cancer Registry in Korea, Central Cancer Registry Center, Ministry of Health and Welfare p42, 2001
  17. Gregorian SK, Battisto JR: Immunosuppression in murine renal cell carcinoma.I. Characterization of extent, severity and sources. Cancer Immunol Immunothe 31(6);325-334, 1990 https://doi.org/10.1007/BF01741403
  18. Medial Research Council Renal Cancer Collaborators: Interferon-$\alpha$ and survival in metastatic renal carcinoma: early results of a randomized controlled trial. Lancet 353;14, 1999 https://doi.org/10.1016/S0140-6736(98)03544-2
  19. Rosenberg SA, Lotze MT, Mull LM: A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med 316;889, 1987 https://doi.org/10.1056/NEJM198704093161501
  20. Gregorian SK., Battisto JR. : Immunosuppression in murine renal cell carcinoma II. Identification of responsible lymphoid cell phenotypes and examination of eliminatin of suppression. Cancer Immunol Immunothe 31(6);335-341, 1990 https://doi.org/10.1007/BF01741404
  21. Divgi CR, Bander NH, Scott AM: Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma. Clin Cancer Res 4;2729, 1998
  22. Grabmaier K, Vissier JLM, De Weuert MCA: Molecular cloning and immunogenicity of renal cell carcinoma-associated antigen G250. Int J Cancer 85;865, 2000 https://doi.org/10.1002/(SICI)1097-0215(20000315)85:6<865::AID-IJC21>3.0.CO;2-Q
  23. Inaba K, Inaba M, Romani N, Aya H, Dequchi M, Ikehara S, Steinman RM: Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med 176(6);1693-1702, 1992 https://doi.org/10.1084/jem.176.6.1693
  24. Ray PK, Raychaudhuri S, Allen P: Mechanism of regression of mammary adenocarcinomas in rats following plasma adsorption over protein A-containing staphylococcus aureus. Cancer Res 42;4970-4974, 1982.
  25. Yoon HL, Singh KP, Ratner S, Reiners Jr JJ: Phorbol ester effects on splenic lymphocyte composition and cytotoxic T cell activities of SSIN mice: a strain deficient in CD8+ T cells. Carcinogenesis 17(12);2617-2624, 1996. https://doi.org/10.1093/carcin/17.12.2617
  26. Lotze, M., Shurin, M., Davis, I., Amoscato, A., and Storkus, W.:Dendritic cell based therapy of cancer. Dendritic Cells in Fundamental and Clinical Immunology. Ricciardi-Castagnoli ed., Plenum Press, New York, USA, 1997
  27. Inaba K, Inaba M, Deguchi M, Hagi K, Yasumizu R, Ikehara S, Muramatsu S, Steinman RM: Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex calss II-negative progenitor in mouse bone marrow. Proc Natl Acad Sci USA 90;3038-3042, 1993 https://doi.org/10.1073/pnas.90.7.3038
  28. Olweus J, BitMansour A, Warnke R: Dendritic cell ontogeny: a human dendritic cell lineage of myeloid origin. Proc Natl Acad Sci USA 94;12551-12556, 1997 https://doi.org/10.1073/pnas.94.23.12551
  29. Steinman RM, Inaba K: Myeloid dendritic cells. J Leuk Biol 66(2);205-208, 1999 https://doi.org/10.1002/jlb.66.2.205
  30. Wu L: Development of thymic and splenic dendritic cell populations from different hemopoietic precursors. Blood 98;3376-3382, 2001 https://doi.org/10.1182/blood.V98.12.3376
  31. Sallusto F, Lanzavecchia A: Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor-. J Exp Med 179;1109, 1994 https://doi.org/10.1084/jem.179.4.1109
  32. Kalinski P, Schuitemarker JH, Hilkens CM, Wierenga EA, Kapsenberg ML: Final maturation of dendritic cells id associated with impaired responsiveness to IFN-gamma and to bacterial IL-12 inducers: decreased ability ofmature dendritic cells to produce IL-12 during the interaction with Th cells. J Immunol 162(6);3231-3236, 1999
  33. Jonuleit H, Kuhn U, Muller G: Pro-inflammatory cytokines and prostaglandines induce maturaton of potent immunostimulatory dendritic cells under feta-calf-serum free conditions. Eur J Immunol 27(12); 3135-3142, 1999 https://doi.org/10.1002/eji.1830271209
  34. Su Z, Dannull J, Heiser A, Yancey D, Pruitt S, Madden J, Coleman D, Niedzwiecki D, Gilboa E, Vieweg J: Imunological and clinical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells. Cancer Res 63;2127-2133, 2003
  35. Oosterwijk-Wakka J, Tiemessen D, Bleumer I, de Varies I, Jongmans W, Adema G, Debruyne F, de Mulder PH, Oosterwijk E, Mulders PF: Vaccination of patients with metastatic renal cell carcinoma with autologous dendritic cells pulsed with autologous tumor antigen in combination with interleukin-2: A phase I study. J Immunother 25(6);500-508, 2002 https://doi.org/10.1097/00002371-200211000-00006
  36. Gitlitz B, Belldegrun A, Zisman A, Chao D, Pantuck A, Hinkel A, Mulders P, Moldawer N, Tso C, Figlin R: A pilot trial of tumor lysate-loaded dendritic cells for the treatment of metastatic renal cell carcinoma. J Immunother 26(5);412-419, 2003 https://doi.org/10.1097/00002371-200309000-00004
  37. Holtl L, Rieser C, Papesh C: Cellular and humoral immune responses in patients with metastatic renal cell carcinoma after vaccination with antigen pulsed dendritic cells. J Urol 161;777, 1999 https://doi.org/10.1016/S0022-5347(01)61767-1