Browse > Article

Oncolytic Vaccinia Virus Expressing 4-1BBL Inhibits Tumor Growth by Increasing CD8+ T Cells in B16F10 Tumor Model  

Lee, Na-Kyung (Department of Biomedical Laboratory Science, Soon Chun Hyang University)
Kim, Hong-Sung (Department of Biomedical Laboratory Science, Korea Nazarene University)
Abstract
Oncolytic viral vectors have shown good candidates for cancer treatment but have many limitations. To improve the therapeutic potential of oncolytic vaccinia virus, we developed a recombinant vaccinia virus expressing the 4-1BBL co-stimulatory molecule or CCL21. 4-1BBL and CCL21 expression was identified by FACS analysis and immunoblotting. rV-4-1BBL vaccination shows significant tumor regression compared to rV-LacZ, but rV-CCL21 shows rapid tumor growth compared to rV-LacZ in the poorly immunogenic B16 murine melanoma model. 4-1BBL expression resulted in the increase of the number of CD8+ T cells and especially the increase of effector (CD62L-CD44+) CD8+ T cells. These data suggest 4-1BBL may be the potential target for enhancement of tumor immunotherapy.
Keywords
4-1BBL; Gene therapy; Vaccine; Vaccinia virus;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Applebaum J, Reynolds S, Knispel J, Oratz R, Shapiro R, Bystryn JC. Identification of melanoma antigens that are immunogenic in humans and expressed in vivo. J Natl Cancer Inst. 1998. 90: 146-149.   DOI   ScienceOn
2 John LB, Howland LJ, Flynn JK, West AC, Devaud C, Duong CP, Stewart TJ, Westwood JA, Guo ZS, Bartlett DL, Smyth MJ, Kershaw MH, Darcy PK. Oncolytic virus and anti-4-1BB combination therapy elicits strong antitumor immunity against established cancer. Cancer Res. 2012. 72: 1651-1660.   DOI
3 Kalbacova M, Spisakova M, Liskova J, Melkova Z. Lytic infection with vaccinia virus activates caspases in a Bcl-2-inhibitable manner. Virus Res. 2008. 135: 53-63.   DOI   ScienceOn
4 Kaufman HL, Cohen S, Cheung K, DeRaffele G, Mitcham J, Moroziewicz D, Schlom J, Hesdorffer C. Local delivery of vaccinia virus expressing multiple costimulatory molecules for the treatment of established tumors. Hum Gene Ther. 2006. 17: 239-244.   DOI   ScienceOn
5 Kaufman HL, Deraffele D, Mitcham J, Moroziewicz D, Cohen SM, Hurst-Wicker KS, Cheung K, Lee DS, Divito J, Voulo M, Donovan J, Dolan K, Manson K, Panicali D, Wang E, Horig H, Marincola FM. Targeting the local tumor microenvironment with vaccinia virus expressing B7.1 for the treatment of melanoma. J Clin Invest. 2005. 115: 1903-1912.   DOI   ScienceOn
6 Kirn DH, Thorne SH. Targeted and armed oncolytic poxviruses: a novel multi-mechanistic therapeutic class for cancer. Nat Rev Cancer. 2009. 9: 64-71.   DOI   ScienceOn
7 Kober J, Leitner J, Klauser C, Woitek R, Majdic O, Stockl J, Herndler-Brandstetter D, Grubeck-Loebenstein B, Reipert BM, Pickl WF, Pfistershammer K, Steinberger P. The capacity of the TNF family members 4-1BBL, OX40L, CD70, GITRL, CD30L and LIGHT to costimulate human T cells. Eur J Immunol. 2008. 38: 2678-2688.   DOI   ScienceOn
8 Kudo-Saito C, Hodge JW, Kwak H, Kim-Schulze S, Schlom J, Kaufman HL. 4-1BB ligand enhances tumor-specific immunity of poxvirus vaccines. Vaccine 2006. 24: 4975-4986.   DOI   ScienceOn
9 McCart JA, Ward JM, Lee J, Hu Y, Alexander HR, Libutti SK, Moss B, Bartlett DL. Systemic cancer therapy with a tumorselective vaccinia virus mutant lacking thymidine kinase and vaccinia growth factor genes. Cancer Res. 2001. 61: 8751-8757.
10 Melero I, Bach N, Hellstrom KE, Aruffo A, Mittler RS, Chen L. Amplification of tumor immunity by gene transfer of the co-stimulatory 4-1BB ligand: synergy with the CD28 costimulatory pathway. Eur J Immunol. 1998. 28: 1116-1121.   DOI   ScienceOn
11 Parato KA, Senger D, Forsyth PA, Bell JC. Recent progress in the battle between oncolytic viruses and tumors. Nat Rev Cancer. 2005. 5: 965-976.
12 Schmidt FI, Bleck CK, Mercer J. Poxvirus host cell entry. Curr Opin Virol. 2012. 2: 20-27.   DOI   ScienceOn
13 Serghides L, Bukczynski J, Wen T, Wang C, Routy JP, Boulassel MR, Sekaly RP, Ostrowski M, Bernard NF, Watts TH. Evaluation of OX40 ligand as a costimulator of human antiviral memory CD8 T cell responses: comparison with B7.1 and 4-1BBL. J Immunol. 2005. 175: 6368-6377.
14 van der Bruggen P, Traversari C, Chomez P, Lurguin C, De Plaen E, Van den Eynde B, Knuth A, Boon T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 1991. 254: 1643-1647.   DOI
15 Sharma S, Yang SK, Hillinger S, Zhu LX, Huang M, Batra RK, Lin JF, Burdick MD, Strieter RM, Dubinett SM. SLC/CCL21-mediated anti-tumor responses require IFN, MIG/CXCL9 and IP-10/CXCL10. Mol Cancer. 2003. 2: 22-27.   DOI
16 Stephan MT, Ponomarev V, Brentjens RJ, Chang AH, Dobrenkov KV, Heller G, Sadelain M. T cell-encoded CD80 and 4-1BBL induce auto- and transcostimulation, resulting in potent tumor rejection. Nat Med. 2007. 13: 1440-1449.   DOI   ScienceOn
17 Thorne SH, Hwang TH, O'Gorman WE, Bartlett DL, Sei S, Kanji F, Brown C, Werier J, Cho JH, Lee DE, Wang Y, Bell J, Kirn DH. Rational strain selection and engineering creates a broad-spectrum, systemically effective oncolytic poxvirus, JX-963. J Clin Invest. 2007. 117: 3350-3358.   DOI   ScienceOn
18 Wilcox RA, Flies DB, Zhu G, Johnson AJ, Tamada K, Chapoval AI, Strome SE, Pease LR, Chen L. Provision of antigen and CD137 signaling breaks immunological ignorance, promoting regression of poorly immunogenic tumors. J Clin Invest. 2002. 109: 651-659.
19 Xu DP, Sauter BV, Huang TG, Meseck M, Woo SL, Chen SH. The systemic administration of Ig-4-1BB ligand in combination with IL-12 gene transfer eradicates hepatic colon carcinoma. Gene Ther. 2005. 12: 1526-1533.   DOI   ScienceOn
20 Yi KH, Nechushtan H, Bowers WJ, Walker GR, Zhang Y, Pham DG, Podack ER, Federoff HJ, Tolba KA, Rosenblatt JD. Adoptively transferred tumor-specific T cells stimulated ex vivo using herpes simplex virus amplicons encoding 4-1BBL persist in the host and show antitumor activity in vivo. Cancer Res. 2007. 67: 10027-10037.   DOI   ScienceOn
21 Zhao Y, Croft M. Dispensable role for 4-1BB and 4-1BBL in development of vaccinia virus-specific CD8 T cells. Immunol Lett. 2012. 141: 220-226.   DOI   ScienceOn