Induction of an effective anti-tumor immune response and tumor regression by combined administration of IL-18 and Apoptin.

作者: Hai Lian , Ningyi Jin , Xiao Li , Zhiqiang Mi , Jingmin Zhang

DOI: 10.1007/S00262-006-0178-Y

关键词:

摘要: Immunization strategies using plasmid DNA can potentially improve humoral and cellular immune responses that protect against cancer infectious diseases. The chicken anemia virus-derived Apoptin protein exhibits remarkable specificity in its ability to induce apoptosis tumor cells, but not normal diploid cells. Interleukin-18 (IL-18) is a Th1-type cytokine has demonstrated potential as biological adjuvant murine models. In this study, we analyzed the anti-tumor mechanism of action simultaneous IL-18 gene transfer C57BL/6 mice bearing Lewis lung carcinoma (LLC). Here report growth established tumors immunized with pAPOPTIN conjunction pIL-18 was significantly inhibited compared empty vector (EV) or alone. Furthermore, immunization elicited strong natural killer activity LLC tumor-specific cytotoxic T lymphocyte (CTL) vitro. addition, cells from lymph nodes vaccinated + secreted high levels Th1 IL-2 IFN-gamma, indicating regression related dominant response. These results demonstrate vaccination together may be novel powerful strategy for immunotherapy.

参考文章(38)
Frederick L. Kiechle, Tadeusz Malinski, Nitric oxide. Biochemistry, pathophysiology, and detection. American Journal of Clinical Pathology. ,vol. 100, pp. 567- 575 ,(1993) , 10.1093/AJCP/100.5.567
Shuji Nakamura, Takeshi Otani, Yoshihiro Ijiri, Ryuichi Motoda, Masashi Kurimoto, Kunzo Orita, IFN-γ-Dependent and -Independent Mechanisms in Adverse Effects Caused by Concomitant Administration of IL-18 and IL-12 The Journal of Immunology. ,vol. 164, pp. 3330- 3336 ,(2000) , 10.4049/JIMMUNOL.164.6.3330
A.B. Sandler, J. Nemunaitis, C. Denham, J. von Pawel, Y. Cormier, U. Gatzemeier, K. Mattson, Ch. Manegold, M.C. Palmer, A. Gregor, B. Nguyen, C. Niyikiza, L.H. Einhorn, Phase III Trial of Gemcitabine Plus Cisplatin Versus Cisplatin Alone in Patients With Locally Advanced or Metastatic Non–Small-Cell Lung Cancer Journal of Clinical Oncology. ,vol. 18, pp. 122- 122 ,(2000) , 10.1200/JCO.2000.18.1.122
K Nakamura, H Okamura, M Wada, K Nagata, T Tamura, Endotoxin-induced serum factor that stimulates gamma interferon production. Infection and Immunity. ,vol. 57, pp. 590- 595 ,(1989) , 10.1128/IAI.57.2.590-595.1989
Diane Fairclough, David Cella, John Kugler, Eric Rowinsky, Michael Jiroutek, David Johnson, Philip Bonomi, KyungMann Kim, Comparison of Survival and Quality of Life in Advanced Non–Small-Cell Lung Cancer Patients Treated With Two Dose Levels of Paclitaxel Combined With Cisplatin Versus Etoposide With Cisplatin: Results of an Eastern Cooperative Oncology Group Trial Journal of Clinical Oncology. ,vol. 18, pp. 623- 631 ,(2000) , 10.1200/JCO.2000.18.3.623
Mark J. Smyth, Masaru Taniguchi, Shayna E. A. Street, The Anti-Tumor Activity of IL-12: Mechanisms of Innate Immunity That Are Model and Dose Dependent Journal of Immunology. ,vol. 165, pp. 2665- 2670 ,(2000) , 10.4049/JIMMUNOL.165.5.2665
Cristina Oro, David Jans, The Tumour Specific Pro-Apoptotic Factor Apoptin (Vp3) from Chicken Anaemia Virus Current Drug Targets. ,vol. 5, pp. 179- 190 ,(2004) , 10.2174/1389450043490631
Mario P Colombo, Giorgio Trinchieri, Interleukin-12 in anti-tumor immunity and immunotherapy Cytokine & Growth Factor Reviews. ,vol. 13, pp. 155- 168 ,(2002) , 10.1016/S1359-6101(01)00032-6
James A Triccas, Lisa Sun, Umaimainthan Palendira, Warwick J Britton, Comparative affects of plasmid-encoded interleukin 12 and interleukin 18 on the protective efficacy of DNA vaccination against Mycobacterium tuberculosis. Immunology and Cell Biology. ,vol. 80, pp. 346- 350 ,(2002) , 10.1046/J.1440-1711.2002.01087.X
Ivan K.H. Poon, Cristina Oro, Manisha M. Dias, Jingpu Zhang, David A. Jans, Apoptin Nuclear Accumulation Is Modulated by a CRM1-Recognized Nuclear Export Signal that Is Active in Normal but not in Tumor Cells Cancer Research. ,vol. 65, pp. 7059- 7064 ,(2005) , 10.1158/0008-5472.CAN-05-1370