IMMUNE NETWORK

  • 제5권3호
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  • Pages.163-171
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  • 2005
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  • 1598-2629(pISSN)
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  • 2092-6685(eISSN)
대한면역학회 (The Korean Association of Immunobiologists)
권호 표지

동종 종양 세포 용해액을 이용한 수지상 세포 항암 백신의 흑색종 폐암 전이 모델에서의 효과 연구

Effect of Dendritic Cell Based Cancer Vaccine Using Allogeneic Tumor Cell Lysate in Melanoma Pulmonary Metastasis Model

  • 이영준 (㈜메디포스트 중앙연구소) ;
  • 김명주 (성균관대학교 의과대학 삼성서울병원 암센터) ;
  • 인소희 (성균관대학교 의과대학 삼성서울병원 암센터) ;
  • 최옥미 (㈜메디포스트 중앙연구소) ;
  • 백소영 (성균관대학교 의과대학 삼성서울병원 암센터) ;
  • 권영도 (㈜메디포스트 중앙연구소) ;
  • 이현아 (성균관대학교 의과대학 삼성서울병원 암센터)
  • Lee, Young-Joon (Medipost Biomedical Research Institute) ;
  • Kim, Myung-Joo (The Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • In, So-Hee (The Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Choi, Ok-Mi (Medipost Biomedical Research Institute) ;
  • Baek, So-Young (The Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kwon, Young-Do (Medipost Biomedical Research Institute) ;
  • Lee, Hyun-Ah (The Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 발행 : 2005.09.30
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초록

Background: To perform the successful dendritic cell-based cancer immunotherapy one of the main issues to be solved is the source of antigen for DC pulsing. Limitations occur by using auto-tumor lysate due to the difficulties obtaining enough tumor tissue(s) quantitatively as well as qualitatively. In this study the possibility of allogeneic tumor cell lysate as a DC pulsing antigen has been tested in mouse melanoma pulmonary me tastasis model. Methods: B16F10 melanoma cells $(1{\timeS}10^5/mouse)$ were inoculated intra venously into the C57BL/6 mouse. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 (1,000 U/ml each) for 7 days and pulsed with lysate of either autologous B16F10 (B-DC), allogeneic K1735 (C3H/He origin; K-DC) or CloneM3 (DBA2 origin; C-DC) melanoma cells for 18 hrs. Pulsed-DCs $(1{\times}10^6/mouse)_{[CGP1]}$ were injected i.p. twice with one week interval starting from the day 1 after tumor cell inoculation. Results: Without observable toxicity, allogeneic tumor cell lysate pulsed-DC induced the significantly better anti-tumor response (tumor scale: $2.7{\pm}0.3,\;0.7{\pm}0.3\;and\;0.3{\pm}0.2$ for saline, B-DC and C-DC treated group, respectively). Along with increased tumor specific lymphocyte proliferations, induction of IFN-${\gamma}$ secretion against both auto- and allo-tumor cell lysates was observed from the DC treated mice. (w/B16F10-lysate: $44.97{\pm}10.31,\;1787.94{\pm}131.18,\;1257.15{\pm}48.27$, w/CloneM3 lysate: 0, $1591.13{\pm}1.83,\;1460.47{\pm}86.05pg/ml$ for saline, B-DC and C-DC treated group, respectively) Natural killer cell activity was also increased in the mice treated with tumor cell lysate pulsed-DC ($8.9{\pm}_{[CGP2]}0.1,\;11.6{\pm}0.8\;and\;12.6{\pm}0.7%$ specific NK activity for saline, B-DC and C-DC treated group, respectively). Conclusion: Conclusively, promising data were obtained that allogeneic-tumor cell lysate can be used as a tumor antigen for DC-based cancer immunotherapy.

키워드

참고문헌

  1. Steinman RM: The dendritic cell system and its role in im nogenicitv, Annu Rev Immunol 9;271-296, 1991 https://doi.org/10.1146/annurev.iy.09.040191.001415
  2. Paglia P, Chiodoni C, Rodolfo M, Colombo MP: Murine dritic cells loaded in vitro with soluble protein prime cyt xic T lymphocytes against tumor antigen in vivo. J Exp Med 183:317-322, 1996 https://doi.org/10.1084/jem.183.1.317
  3. Brossart P, Goldrath A W, Butz EA, Martin S, Bevan MJ: rus-mediated delivery of antigenic epitopes into dendti cells as a means to induce CTL. J Immunol 158;3270-3276, 1997
  4. Brossart P, Bevan MJ: Presentation of exogenous protein tigens on major histocompatibility complex class I molecu by dendritic cells: pathway of presentation and regulation cytokines. Blood 90;1594-1599, 1997
  5. Banchereau J. Steinman RM: Dendritic cells and the COnt of immunity. Nature 392;245-252, 1998 https://doi.org/10.1038/32588
  6. Cella M, Sallusto F, Lanzavecchia A: Origin, maturation antigen presenting function of dendritic cells. Curr Opin Immunol 9;10-16, 1997 https://doi.org/10.1016/S0952-7915(97)80153-7
  7. Porgador A, Gilhoa E: Bone marrow-generated dendritic c pulsed with a class I restricted peptide are potent indue of cytotoxic T lymphocytes. J Exp Med 182;255-260, 1995 https://doi.org/10.1084/jem.182.1.255
  8. Zitvogel L, Mayordomo JI, Tiandrawan T, DeLeo AB, Cl MR, Lotze MT: Therapy of murine tumors with turnor-p tide pulsed dendritic cells: dependence on T cells, B7 cos mulation. and T helper cell l-associated cytokines. J Exp Med 183;87-97, 1996 https://doi.org/10.1084/jem.183.1.87
  9. Bevan MJ: Cross-priming for a secondary cytotoxic respo to minor H antigen with H-2 congenic cells which do cross-react in the cytotoxic assay. J Exp Med 143;1283-128 1976 https://doi.org/10.1084/jem.143.5.1283
  10. Huang AY, Golumbek P, Ahmadzadeh M, Jaffee E, Pard D, Levitsky H: Role of bone marrow-derived cells in p senting MHC class I-restricted tumor antigens. Science 264; 961-965, 1994 https://doi.org/10.1126/science.7513904
  11. Reis e Sousa C, Germain RN: Major histocompatibility c plex class I presentation of peptides derived from soluble e ogenous antigen by a subset of cells engaged in phagocyte J Exp Med 182;841-851, 1995 https://doi.org/10.1084/jem.182.3.841
  12. Norbury CC, Chambers BJ. Prescott AR, Liunggren H Watts C: Constitutive macropinocytosis allows TAP-dep dent presentation of exogenous antigen on class I MHC molecules by bone marrow derived dendritic cells. Eur J Immunol 27:280-288. 1997 https://doi.org/10.1002/eji.1830270141
  13. Carbone FR. Kurts C. Bennett SR. Miller TF. Heath W Cross-presentation: a general mechanism for CTL immun and tolerance. Immunol Today 19;368-373. 1998 https://doi.org/10.1016/S0167-5699(98)01301-2
  14. Inaba K. Inaba M. Romani N. Aya H. Dequchi M. Ikeh S. Steinman RM: Generation of large numbers of dendr cells from mouse bone marrow cultures supplemented w granulocyte/macrophage colony-stimulating factor. J Exp Med 176:1693-1702. 1992 https://doi.org/10.1084/jem.176.6.1693
  15. Sallusto F. Lanzavecchia A: Efficient presentation of solu antigen by cultured human dendritic cells is maintained zranulocvte/rnacrouhaee colony-stimulating factor plus in leukin-4 and downrezulated by tumor necrosis factor- $\alpha$. J Exp Med 179;1109-1118. 1994 https://doi.org/10.1084/jem.179.4.1109
  16. Romani N. Gruner S. Branz D. Karnozen E. Lenz A. Tr kenbacher B: Proliferating dendritic cell progenitors in man blood. J Exp Med 180;83-93. 1994 https://doi.org/10.1084/jem.180.1.83
  17. Hsu FT. Benike C. Faznoni F. Liles TM. Czerwinski D. T B: Vaccination of patients with B-cell lymphoma using au lozous antigen-pulsed dendritic cells. Nat Med 2:52-58. 1996 https://doi.org/10.1038/nm0196-52
  18. Nestle Fa. Aliiazic S. Gilliet M. Sun Y. Grabbe S. Dum R: Vaccination of melanoma patients with peptide- or tum lysate-pulsed dendritic cells. Nat Med 4;328-332. 1998 https://doi.org/10.1038/nm0398-328
  19. Murphy G. Tioa B. Ragde H. Kenny G. Boynton A: Ph I clinical trial: T-cell therapy for prostate cancer using auto gous dendritic cells pulsed with HLA-A0201 specific peptid from prostate-specific membrane antigen. Prostate 29;371-380. 1996 https://doi.org/10.1002/(SICI)1097-0045(199612)29:6<371::AID-PROS5>3.0.CO;2-B
  20. Murphy GP. Tjoa BA. Simmons ST. Tarisch T. Bowes V Ragde H: Infusion of dendritic cells pulsed with HLA-A specific prostate-specific membrane antigen oeotides: a pha II prostate vaccine trial involving patients with hormone fractory metastatic disease. Prostate 38:73-78. 1999 https://doi.org/10.1002/(SICI)1097-0045(19990101)38:1<73::AID-PROS9>3.0.CO;2-V
  21. Morse MA. Denz Y. Coleman D. Hull S. Kitrell-Fisher Nair S: A phase I study of active immunotherapy with ca noembrvonic antigen peptide (CAP-I)-pulsed. autologous man cultured dendritic cells in patients with metastatic rna nancies expressing carcinoembryonic antigen. Clin Cancer Res 5:1331-1338. 1999
  22. Thurner B. Haendle I, Roger C. Dieckmann D. Keikavo P. Tonuleit H: Vaccination with Mage-3A1 peptide oul mature. monocyte-derived dendritic cells expands specific totoxic T cells and induces regression of some metastases advanced stage N melanoma. J Exp Med 190;1669-1678, 1999 https://doi.org/10.1084/jem.190.11.1669
  23. Brossart P. Wirths S. Stuhler G. Reichardt VL, Kanz L, Br ger W: Induction of cytotoxic T-lymphocyte responses vivo after vaccinations with peptide-pulsed dendritic cells. Blood 96;3102-3108. 2000
  24. Holtl L, Reiser C. Papesh C. Ramoner R. Herold M. Klo H: Cellular and humoral immune responses in patients w metastatic renal cell carcinoma after vaccination with anti pulsed dendritic cells. J Urol 161;777-782. 1999 https://doi.org/10.1016/S0022-5347(01)61767-1
  25. Schott M. Feldkamp J. Schattenbera D. Krueger T. Dotzen th C. Seissler T: Induction of cellular immunity in a para roid carcinoma treated with tumor lysate pulsed dendr cells. Eur J Endocrinol 142;300-306. 2000 https://doi.org/10.1530/eje.0.1420300
  26. Geiger JD. Hutchinson RJ. Hohenkirk LF. McKenna E Yanik GA. Levine JE: Vaccination of pediatric solid tum patients with tumor lysate-pulsed dendritic cells can expa specific T cells and mediate tumor regression. Cancer Res 61:8513-8519. 2001
  27. Hernando Il. Park TW. Kubler K. Offerzeld R. Schlebu H. Bauknecht T: Vaccination with autologous tumor ant pulsed dendritic cells in advanced gynaecological malign cies: clinical and immunological evaluation of a phase I tr Cancer Immunol Immunother 51;45-52, 2002 https://doi.org/10.1007/s00262-001-0255-1
  28. Azuma T. Horie S, Tomita K. Takahashi T, Tanaka Y. Ka wase K: Dendritic cell imrnunotheranv for patients with tastatic renal cell carcinoma: University of Tokyo experie Int J Urology 9;340-346, 2002 https://doi.org/10.1046/j.1442-2042.2002.00477.x
  29. Amoscato AA, Prenovits DA. Lotz MT: Rapid extracell degradation of svnthetic class I oeotides by human dendr cells. J Immunol 161;4023-4032. 1998
  30. Souberbielle BE, Westbv M. Ganz S. Kavaza T. Mendes Morrow WTW, Dalgleish AG: Comparison of four strate for tumour vaccination in the B16-F10 melanoma mod Gene Ther 5;1447-1454. 1998 https://doi.org/10.1038/sj.gt.3300747
  31. Melcher A, Todryk S, Bateman A, Chong H. Lemoine Vile RG: Adoptive transfer of immature dendritic cells w autologous or allogeneic tumor cells generates systemic an tumor imrnunity. Cancer Res 59;2802-2805, 1999
  32. Berard F, Blanco P, Davoust J. Neidhart-Berard EM, Nou Shirazi M, Taouet N: Cross-priming of naive CD8 T c against melanoma antigens using dendritic cells loaded w killed allogeneic melanoma cells. J Exp Med 192;1535-1543, 2000 https://doi.org/10.1084/jem.192.11.1535
  33. Jenne L Arrighi JF. Tonuleit H, Saurat JH, Hauser C: D dritic cells containing apoptotic melanoma cells prime hum $CD8^+$ T cells for efficient tumor cell lysis. Cancer Res 60;4446-4452, 2000
  34. Holtl L Zelle-Rieser C. Gander H. Papesh C. Ramoner Bartsch G: Immunotherapv of metastatic renal cell carcino with autologous tumor Ivsate-nulsed dendritic cells. Scient Program and Abstract of 7th International Symposium Dendritic Cells, p145. 2002
  35. Bercovici N, Massicard S, Baron V, Pauillac F. Hamon Agrawal S: Immune responses in patients with metastatic m lanoma immunized with autologous DC loaded with an a zeneic melanoma cell lvsate. Scientific Program and Abstr of 7th International Symposium on Dendritic Cells, p1 2002
  36. Dematos P, Abdel-Wahab Z. Vervaert C, Hester D, Seiz H: Pulsing of dendritic cells with cell lvsates from either B melanoma or MCA-106 fibrosarcoma vields eouallv dffect vaccines against B16 tumors in mice. J Surg Oncol 68;79-91, 1998 https://doi.org/10.1002/(SICI)1096-9098(199806)68:2<79::AID-JSO3>3.0.CO;2-H
  37. Yoon HL Singh K, Ratner S, Reiners TT: Phorbol ester fects on splenic lvmphocvte composition and cytotoxic T activities of SSIN mice: a strain deficient in $CD8^+$ T cells. Carcinogenesis 17:2617-2624. 1996 https://doi.org/10.1093/carcin/17.12.2617
  38. Kemp R. Ronchese F: Tumor-specific Tcl, but not Tc2, c deliver protective antitumor immunity. J Immunol 167;6 6502. 2001
  39. Green EL: Handbook on Geneticallv Standardized JAX M New York. McGraw-Hill pp521-562, 1977
  40. Kripke ML: Speculations on the role of ultraviolet radiat in the development of malignant melanoma. J Natl Cancer Inst 63;541-548. 1979 https://doi.org/10.1093/jnci/63.3.541
  41. Cloudman AM: The effect of an extra-chromosomal influ ce upon transplanted spontaneous tumors in mice. Scien 93;380-381. 1941 https://doi.org/10.1126/science.93.2416.380
  42. Peter L Mezzacasa A. LeDonne P. Dummer R. Hemmi Comparative analvsis of immunocritical melanoma marker the mouse melanoma cell lines B16, K1735 and S91-M3. Melanoma Res 11;21-30, 2001 https://doi.org/10.1097/00008390-200102000-00003
  43. Palucka K. Banchereau T: Dendritic cells: a link between nate and adaptive imrnunity. J Clin Immunol 19:12-25, 1999 https://doi.org/10.1023/A:1020558317162
  44. Palucka K, Banchereau J: Linkinz innate and adaptive immnity, Nat Med 5;868-870. 1999 https://doi.org/10.1038/11303
  45. Fernandez N et al: Dendritic cells directlv trigger NK cell fu tions: Cross-talk relevant in innate anti-tumor immune sponses in vivo. Nature Medicine 5;405-410, 1999 https://doi.org/10.1038/7403