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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

이현아|김명주|백소영|권영도|이영준|인소희|최옥미
대한면역학회 (The Korean Association of Immunologists)|2005.09|Immune Network|제5권 제3호|pp. 163-171

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Abstract

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 metastasis model. Methods: B16F10 melanoma cells (1 105/mouse) were inoculated intravenously 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 (1 106/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 0.3, 0.7 0.3 and 0.3 0.2 for saline, B-DC and C-DC treated group, respectively). Along with increased tumor specific lymphocyte proliferations, induction of IFN-γ secretion against both auto- and allo-tumor cell lysates was observed from the DC treated mice. (w/B16F10-lysate: 44.97 10.31, 1787.94 131.18, 1257.15 48.27, w/CloneM3 lysate: 0, 1591.13 1.83, 1460.47 86.05 pg/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 [CGP2]0.1, 11.6 0.8 and 12.6 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.

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