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http://dx.doi.org/10.7314/APJCP.2013.14.2.987

Exosomes from CIITA-Transfected CT26 Cells Enhance Anti-tumor Effects  

Fan, Wen (First Affiliated Hospital of Yangtze University)
Tian, Xing-De (First Affiliated Hospital of Yangtze University)
Huang, E. (First Affiliated Hospital of Yangtze University)
Zhang, Jia-Jun (First Affiliated Hospital of Yangtze University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.14, no.2, 2013 , pp. 987-991 More about this Journal
Abstract
Aim: To study anti-tumor effects of exosomes from class II transactivator (CIITA) gene transfected CT26 cells. Methods: In this study, we established an MHC class II molecule-expressing murine colon cancer cell line (CT26-CIITA) by transduction of the CIITA gene. Immune effects in vitro and tumor protective results in vivo were tested and monitored. Results: Exosomes from CT26-CIITA cells were found to contain a high level of MHC class II protein. When loaded on dendritic cells (DCs), exosomes from CT26-CIITA cells significantly increased expression of MHC class II molecules, CD86 and CD80, as compared to exosomes from CT26 cells. In vitro assays using co-culture of immunized splenocytes and exosome-loaded DCs demonstrated that CIITA-Exo enhanced splenocyte proliferation and IFN-${\gamma}$ production of CD4+T cells, while inhibiting IL-10 secretion. In addition, compared to exosomes from CT26 cells, CT26-CIITA-derived exosomes induced higher TNF-${\alpha}$ and IL-12 mRNA levels. A mouse tumour preventive model showed that CT26-CIITA derived exosomes significantly inhibited tumour growth in a dose-dependent manner and significantly prolonged the survival time of tumour-bearing mice. Conclusion: Our findings indicate that CT26-CIITA-released exosomes are more efficient to induce anti-tumour immune responses, suggesting a potential role of MHC class II-containing tumour exosomes as cancer vaccine candidates.
Keywords
Exosomes; CIITA transfection; IFN-${\gamma}$ production; cancer vaccine;
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1 Martin-Jaular L, Nakayasu ES, Ferrer M, et al (2011). Exosomes from Plasmodium yoelii-infected reticulocytes protect mice from lethal infections. PLoS One, 6, e26588.   DOI
2 Mathias RA, Lim JW, Ji H, et al (2009). Isolation of extracellular membranous vesicles for proteomic analysis. Methods Mol Biol, 528, 227-42.   DOI   ScienceOn
3 Morse MA, Secord AA, Blackwell K, et al (2011). MHC class I-presented tumor antigens identified in ovarian cancer by immunoprot-eomic analysisare targets for T-cell responses against breast and ovarian cancer. Clin Cancer Res, 17, 3408-19.   DOI
4 Mortara L, Castellani P, Meazza R, et al (2006). CIITA-induced MHC class II expression in mammary adenocarcinoma leads to a Th1 polarization of the tumor microenvironment, tumor rejection, and specific antitumor memory. Clin Cancer Res, 12, 3435-43.   DOI   ScienceOn
5 Nazarenko I, Rana S, Baumann A, et al (2010). Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation. Cancer Res, 70, 1668-78.   DOI
6 Rountree RB, Mandl SJ, Nachtwey JM, et al (2011). Exosome targeting of tumor antigens expressed by cancer vaccines can improve antigen immunogenicity and therapeutic efficacy. Cancer Res, 71, 5235-44.   DOI
7 Sartoris S, Brendolan A, Degola A, et al (2000). Analysis of CIITA encoding AIR-1 gene promoters in insulin-dependent diabetes mellitus and rheumatoid arthritis patients from the northeast of Italy: absence of sequence variability. Hum Immunol, 61, 599-604.   DOI   ScienceOn
8 Schnitzer JK, Berzel S, Fajardo-Moser M, et al (2010). Fragments of antigen-loaded dendritic cells (DC) and DC-derived exosomes induce protective immunity against Leishmania major. Vaccine, 28, 5785-93.   DOI   ScienceOn
9 Silva J, Garcia V, Rodriguez M, et al (2012). Analysis of exosome release and its prognostic value in human colorectal cancer. Genes Chromosomes Cancer, 51, 409-18.   DOI   ScienceOn
10 Southcombe J, Tannetta D, Redman C, et al (2011). The immunomodulatory role of syncytiotrophoblast microvesicles. PLoS One, 6, e20245.   DOI
11 Tan A, De La Pena H, Seifalian AM (2010). The application of exosomes as a nanoscale cancer vaccine. Int J Nanomedicine, 5, 889-900.
12 van Niel G, Raposo G, Candalh C, et al (2001). Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology, 121, 337-49.   DOI   ScienceOn
13 Andre F, Chaput N, Schartz NE, et al (2004). Exosomes as potent cell-free peptide-based vaccine. I. Dendritic cell-derived exosomes transfer functional MHC class I/peptide complexes to dendritic cells. J Immunol, 172, 2126-36.   DOI
14 Verweij FJ, van Eijndhoven MA, Hopmans ES, et al (2011). LMP1 association with CD63 in endosomes and secretion via exosomes limits constitutive NF-${\kappa}B$ activation. EMBO J, 30, 2115-29.   DOI   ScienceOn
15 Viaud S, Thery C, Ploix S, et al (2010). Dendritic cell-derived exosomes for cancer immunotherapy: what's next? Cancer Res, 70, 1281-5.   DOI   ScienceOn
16 Wiley RD, Gummuluru S (2006). Immature dendritic cell-derived exosomes can mediate HIV-1 trans infection. Proc Natl Acad Sci USA, 103, 738-43.   DOI   ScienceOn
17 Bobrie A, Colombo M, Raposo G, et al (2011). Exosome secretion: molecular mechanisms and roles in immune responses. Traffic, 12, 1659-68.   DOI   ScienceOn
18 Caby MP, Lankar D, Vincendeau-Scherrer C, et al (2005). Exosomal-like vesicles are present in human blood plasma. Int Immunol, 17, 879-87.   DOI   ScienceOn
19 Chaput N, Thery C (2011). Exosomes: immune properties and potential clinical implementations. Semin Immunopathol, 33, 419-40.   DOI   ScienceOn
20 Cheng Y, Sanderson C, Jones M, et al (2012). Low MHC class II diversity in the Tasmanian devil (Sarcophilus harrisii). Immunogenetics, 64, 525-33.   DOI   ScienceOn
21 Cho JA, Lee YS, Kim SH, et al (2009). MHC independent anti-tumor immune responses induced by Hsp70-enriched exosomes generatetumor regression in murine models. Cancer Lett, 275, 256-65.   DOI   ScienceOn
22 de Vrij J, Maas SL, Hegmans JP, et al (2011).[Exosomes and cancer]. Ned Tijdschr Geneeskd, 155, A3677.
23 Hao S, Yuan J, Xiang J (2007). Nonspecific $CD4(^{+})$ T cells with uptake of antigen-specific dendritic cell-released exosomes stimulate antigen-specific $CD8(^{+})$ CTL responses and long-term T cell memory. J Leukoc Biol, 82, 829-38.   DOI   ScienceOn
24 Filipazzi P, Burdek M, Villa A, et al (2012). Recent advances on the role of tumor exosomes in immunosuppression and disease progression. Semin Cancer Biol, 22, 342-9.   DOI   ScienceOn
25 Frangione V, Mortara L, Castellani P, et al (2010).CIITA-driven MHC-II positive tumor cells: preventive vaccines and superior generators of antitumor $CD4_{+}$ T lymphocytes for immunotherapy. Int J Cancer, 127, 1614-24.   DOI   ScienceOn
26 Gastpar R, Gehrmann M, Bausero MA, et al (2005). Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res, 65, 5238-47.   DOI   ScienceOn
27 Luketic L, Delanghe J, Sobol PT, et al (2007). Antigen presentation by exosomes released from peptide-pulsed dendritic cells is not suppressed by the presence of active CTL. J Immunol, 179, 5024-32.   DOI
28 Lv LH, Wan YL, Lin Y, et al (2012).Anticancer drugs cause release of exosomes with heat shock proteins from human hepatocellular carcinoma cells that elicit effective natural killer cell anti-tumor responses in vitro. J Biol Chem, 287, 15874-85.   DOI