Intradermal immunization with combined baculovirus and tumor cell lysate induces effective antitumor immunity in mice

Kawahara,Mamoru; Takaku,Hiroshi

doi:10.3892/ijo.2013.2125

Intradermal immunization with combined baculovirus and tumor cell lysate induces effective antitumor immunity in mice

Authors:
- Mamoru Kawahara
- Hiroshi Takaku
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Affiliations: Research and Development Department, Japan BCG Laboratory, Kiyose, Tokyo 204-0022, Japan, Department of Life and Environmental Sciences, Chiba Institute of Technology, Narashino, Chiba 275-0016, Japan
Published online on: October 4, 2013 https://doi.org/10.3892/ijo.2013.2125
Pages: 2023-2030

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Abstract

Although tumor lysate contains all the potential helper and killer epitopes capable of stimulating T cells, it is difficult to use as a cancer vaccine because it suppresses dendritic cell (DC) function. We report that wild-type baculovirus possesses an adjuvant effect to improve the immunogenicity of tumor lysate. When mice were administered CT26 tumor cell lysate combined with baculovirus intradermally, antitumor immunity was induced and rejection of CT26 tumor growth was observed in 40% of the immunized mice. In contrast, such antitumor immunity was not elicited in mice inoculated with tumor cell lysate or baculovirus alone. In tumor-bearing mice, which had previously received the combined baculovirus and tumor lysate vaccine, the established tumors were completely eradicated by administering a booster dose of the combined vaccine. This antitumor effect was attributed to tumor-specific T cell immunity mediated primarily by CD8+ T cells. Baculovirus also strongly activated DCs loaded with tumor lysate. Increased interleukin (IL)-6 and IL-12p70 production were also observed in DCs co-cultured with tumor cell lysate and baculovirus. Our study demonstrates that combined baculovirus and tumor lysate vaccine can effectively stimulate DCs to induce acquired antitumor immunity.

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1.	Paoletti X, Burzykowski T, Michiels S, Ohashi Y, Pignon JP, Rougier P, Sakamoto J, Sargent D, Sasako M, Van Cutsem E and Buyse M: Benefit of adjuvant chemotherapy for resectable gastric cancer: a meta-analysis. JAMA. 303:1729–1737. 2010. View Article : Google Scholar : PubMed/NCBI
2.	Ochsenbein AF: Principles of tumor immunosurveillance and implications for immunotherapy. Cancer Gene Ther. 9:1043–1055. 2002. View Article : Google Scholar : PubMed/NCBI
3.	Kirkwood JM, Butterfield LH, Tarhini AA, Zarour H, Kalinski P and Ferrone S: Immunotherapy of cancer in 2012. CA Cancer J Clin. 62:309–335. 2012. View Article : Google Scholar
4.	Rosenberg SA, Yang JC and Restifo NP: Cancer immunotherapy: moving beyond current vaccines. Nat Med. 10:909–915. 2004. View Article : Google Scholar : PubMed/NCBI
5.	Toes RE, Blom RJ, Offringa R, Kast WM and Melief CJ: Enhanced tumor outgrowth after peptide vaccination. Functional deletion of tumor-specific CTL induced by peptide vaccination can lead to the inability to reject tumors. J Immunol. 156:3911–3918. 1996.PubMed/NCBI
6.	Toes RE, Offringa R, Blom RJ, Melief CJ and Kast WM: Peptide vaccination can lead to enhanced tumor growth through specific T-cell tolerance induction. Proc Natl Acad Sci USA. 93:7855–7860. 1996. View Article : Google Scholar : PubMed/NCBI
7.	Muraoka D, Kato T, Wang L, Maeda Y, Noguchi T, Harada N, Takeda K, Yagita H, Guillaume P, Luescher I, Old LJ, Shiku H and Nishikawa H: Peptide vaccine induces enhanced tumor growth associated with apoptosis induction in CD8⁺ T cells. J Immunol. 185:3768–3776. 2010. View Article : Google Scholar : PubMed/NCBI
8.	Bour H, Horvath C, Lurquin C, Cerottini JC and MacDonald HR: Differential requirement for CD4 help in the development of an antigen-specific CD8⁺ T cell response depending on the route of immunization. J Immunol. 160:5522–5529. 1998.PubMed/NCBI
9.	Pardoll DM and Topalian SL: The role of CD4⁺ T cell responses in antitumor immunity. Curr Opin Immunol. 10:588–594. 1998.
10.	Toes RE, Ossendorp F, Offringa R and Melief CJ: CD4 T cells and their role in antitumor immune responses. J Exp Med. 189:753–756. 1999. View Article : Google Scholar : PubMed/NCBI
11.	Janssen EM, Lemmens EE, Wolfe T, Christen U, von Herrath MG and Schoenberger SP: CD4⁺ T cells are required for secondary expansion and memory in CD8⁺ T lymphocytes. Nature. 421:852–856. 2003.PubMed/NCBI
12.	Shedlock DJ and Shen H: Requirement for CD4 T cell help in generating functional CD8 T cell memory. Science. 300:337–339. 2003. View Article : Google Scholar : PubMed/NCBI
13.	Lizée G, Rasvanyi LG, Overwijik WW and Hwu P: Immunosuppression in melanoma immunotherapy: potential opportunities for intervention. Clin Cancer Res. 12:S2359–S2365. 2006.PubMed/NCBI
14.	Jackson AM, Mulcathy LA, Zhu XW, O’Donnell D and Patel PM: Tumor-mediated disruption of dendritic cell function: inhibiting the MEK1/2-p44/42 axis restores IL-12 production and Th1-generation. Int J Cancer. 123:623–632. 2008. View Article : Google Scholar : PubMed/NCBI
15.	Yang DH, Park JS, Jin CJ, Kang HK, Nam JH, Rhee JH, Kim YK, Chung SY, Choi SJN, Kim HJ, Chung IJ and Lee JJ: The dysfunction and abnormal signaling pathway of dendritic cells loaded by tumor antigen can be overcome by neutralizing VEGF in multiple myeloma. Leuk Res. 33:665–670. 2009. View Article : Google Scholar : PubMed/NCBI
16.	Schnurr M, Toy T, Stoitzner P, Cameron P, Shin A, Beecroft T, Davis ID, Cebon J and Maraskovsky E: ATP gradients inhibit the migratory capacity of specific human dendritic cell types: implications for P2Y11 receptor signaling. Blood. 102:613–620. 2003. View Article : Google Scholar : PubMed/NCBI
17.	Pinzon-Charry A, Maxwell T and Lopez JA: Dendritic cell dysfunction in cancer: a mechanism for immunosuppression. Immunol Cell Biol. 83:451–461. 2005. View Article : Google Scholar
18.	Bennaceur K, Popa I, Portoukalian J, Bethier-Vergnes O and Peguet-Navarro J: Melanoma-derived gangliosides impair migratory and antigen-presenting function of human epidermal Langerhans cells and induce their apoptosis. Int Immunol. 18:879–886. 2006. View Article : Google Scholar
19.	Stewart LM, Hirst M, López-Ferber M, Merryweather AT, Cayley PJ and Possee RD: Construction of an improved baculovirus insecticide containing an insect-specific toxin gene. Nature. 352:85–88. 1991. View Article : Google Scholar : PubMed/NCBI
20.	Jennifer SC, Mark LH, Trevor W, Rosemary SH, David G, Bernadette MG, Timothy MC, Robert DP, Cayley PJ and Bishop DHL: Field trial of a genetically improved baculovirus insecticide. Nature. 370:138–140. 1994. View Article : Google Scholar
21.	Matsuura Y, Possee RD, Overton HA and Bishop DHL: Baculovirus expression vectors: the requirements for high level expression of proteins, including glycoproteins. J Gen Virol. 68:1233–1250. 1987. View Article : Google Scholar : PubMed/NCBI
22.	Luckow VA and Summers MD: Trends in the development of baculovirus expression vectors. Biotechnology. 6:47–55. 1988. View Article : Google Scholar
23.	Hofmann C, Sandig V, Gennings G, Rudolph M, Schlag P and Strauss M: Efficient gene transfer into human hepatocytes by baculovirus vectors. Proc Natl Acad Sci USA. 92:10099–10103. 1995. View Article : Google Scholar : PubMed/NCBI
24.	Boyce FM and Bucher NLR: Baculovirus-mediated gene transfer into mammalian cells. Proc Natl Acad Sci USA. 93:2348–2352. 1996. View Article : Google Scholar : PubMed/NCBI
25.	Sandig V and Strauss M: Liver-directed gene transfer and application to therapy. J Mol Med. 74:205–212. 1996. View Article : Google Scholar : PubMed/NCBI
26.	Pieroni L and La Monica N: Towards the use of baculovirus as a gene therapy vector. Curr Opin Mol Ther. 3:464–467. 2001.PubMed/NCBI
27.	Kost TA and Condreay JP: Recombinant baculoviruses as mammalian gene-delivery vectors. Trends Biotechnol. 20:173–180. 2002. View Article : Google Scholar : PubMed/NCBI
28.	Gronowski AM, Hilbert DM, Sheehan KCF, Garotta G and Schreiber RD: Baculovirus stimulates antiviral effects in mammalian cells. J Virol. 73:9944–9951. 1999.PubMed/NCBI
29.	Beck NB, Sidhu JS and Omiecinski CJ: Baculovirus vectors repress phenobarbital-mediated gene induction and stimulate cytokine expression in primary cultures of rat hepatocytes. Gene Ther. 7:1274–1283. 2000. View Article : Google Scholar : PubMed/NCBI
30.	Kitajima M, Abe T, Miyano-Kurosaki N, Taniguchi M, Nakayama T and Takaku H: Induction of natural killer cell-dependent antitumor immunity by the Autographa californica multiple nuclear polyhedrosis virus. Mol Ther. 16:261–268. 2008. View Article : Google Scholar : PubMed/NCBI
31.	Suzuki T, Chang MO, Kitajima M and Takaku H: Baculovirus activates murine dendritic cells and induces non-specific NK cell and T cell immune responses. Cell Immunol. 262:35–43. 2010. View Article : Google Scholar : PubMed/NCBI
32.	Suzuki T, Chang MO, Kitajima M and Takaku H: Induction of antitumor immunity against mouse carcinoma by baculovirus-infected dendritic cells. Cell Mol Immunol. 7:440–446. 2010. View Article : Google Scholar : PubMed/NCBI
33.	Schöttker B and Schmidt-Wolf IGH: Pulsing with blast cell lysate or blast-derived total RNA reverses the dendritic cell-mediated cytotoxic activity of cytokine-induced killer cells against allogeneic acute myelogenous leukemia cells. Ger Med Sci. doi: 10.3205/000141. URN: urn:nbn:de:0183-0001410. 2011.
34.	Reis e Sousa C: Dendritic cells in a mature age. Nat Rev Immunol. 6:476–483. 2006.PubMed/NCBI
35.	Pasare C and Medzhitov R: Toll pathway-dependent blockade of CD4⁺CD25⁺ T cell-mediated suppression by dendritic cells. Science. 299:1033–1036. 2003. View Article : Google Scholar : PubMed/NCBI
36.	Shevach EM: Regulatory T cells in autoimmmunity^*. Annu Rev Immunol. 18:423–449. 2000. View Article : Google Scholar
37.	Maloy KJ and Powrie F: Regulatory T cells in the control of immune pathology. Nat Immunol. 2:816–822. 2001. View Article : Google Scholar : PubMed/NCBI
38.	Piccirillo CA and Shevach EM: Cutting edge: control of CD8⁺ T cell activation by CD4⁺CD25⁺ immunoregulatory cells. J Immunol. 167:1137–1140. 2001.PubMed/NCBI
39.	Sakaguchi S: Naturally arising Foxp3-expressing CD25⁺CD4⁺ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol. 6:345–352. 2005. View Article : Google Scholar : PubMed/NCBI
40.	Turk MJ, Guevara-Patiño JA, Rizzuto GA, Engelhorn ME, Sakaguchi S and Houghton AN: Concomitant tumor immunity to a poorly immunogenic melanoma is prevented by regulatory T cells. J Exp Med. 200:771–782. 2004. View Article : Google Scholar : PubMed/NCBI
41.	Yu P, Lee Y, Liu W, Krausz T, Chong A, Schreiber H and Fu YX: Intratumor depletion of CD4⁺ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. J Exp Med. 201:779–791. 2005.PubMed/NCBI
42.	Tani H, Nishijima M, Ushijima H, Miyamura T and Matsuura Y: Characterization of cell-surface determinants important for baculovirus infection. Virology. 279:343–353. 2001. View Article : Google Scholar : PubMed/NCBI
43.	Akira S, Takeda K and Kaisho T: Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol. 2:675–680. 2001. View Article : Google Scholar : PubMed/NCBI