Abstract:
:Dendritic cell (DC)-based immunotherapy has recently demonstrated a great potential for clinical applications; however, additional progress in the methods of tumor-specific antigen delivery to DCs is necessary for the further development of anti-tumor vaccines. To this end, a capsid-optimized adeno-associated virus serotype 6 (AAV6-T492V+S663V) vector was developed by site-directed mutagenesis of surface-exposed serine (S) and threonine (T) residues, which have a critical role in intracellular trafficking of AAV vectors. This double-mutant AAV6 vector had ∼ 5-fold greater transduction efficiency in monocyte-derived DCs (moDCs) compared with wild-type (WT)-AAV6 vectors. The increase in the transduction efficiency correlated with the improved nuclear translocation of AAV6-T492V+S663V over that of the WT-AAV6 vector. Additional studies of the CD11c promoter identified critical regulatory elements that fit into the AAV expression cassette and drive EGFP expression in moDCs. Development of a chimeric promoter (chmCD11c) that contains functional modules of CD11c and a Simian virus (SV40) enhancer element dramatically increased the EGFP expression in moDCs. MoDCs transduced by the capsid-optimized AAV6 vector carrying human prostate-specific antigen (hPSA) driven by CBA (AAV6-T492V+S663V-CBA-hPSA) or chmCd11c (AAV6-T492V+S663V-chmCD11c-hPSA) generated specific T-cell clone proliferation and superior cytotoxic T lymphocytes (CTLs) with higher killing capability against human prostate adenocarcinoma cells, LNCaP, compared with WT-AAV6 induced CTLs. Taken together, these studies suggest that optimization of capsid and promoter components of AAV vectors can be a useful approach for efficient targeting of moDCs and may prove to be a promising tool for cancer immunotherapy.
journal_name
Immunol Cell Bioljournal_title
Immunology and cell biologyauthors
Pandya J,Ortiz L,Ling C,Rivers AE,Aslanidi Gdoi
10.1038/icb.2013.74subject
Has Abstractpub_date
2014-02-01 00:00:00pages
116-23issue
2eissn
0818-9641issn
1440-1711pii
icb201374journal_volume
92pub_type
杂志文章abstract::Irradiated malaria sporozoites induce better protection than viable untreated sporozoites. We observed early differences between irradiated and viable untreated sporozoites in priming responses in vivo to a protective CD8 T-cell epitope, pb9, of the circumsporozoite protein of Plasmodium berghei. Sporozoites were proc...
journal_title:Immunology and cell biology
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abstract::Lymphocytes exchanged rapidly and extensively between mutually tolerant, allogeneic rats following surgical parabiosis. Tolerated allogeneic cells persisted for an extended period in parabiotic partners after separation. A rapid exchange of cells was also observed between parabiosed syngeneic pairs of normal and allog...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.1987.29
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journal_title:Immunology and cell biology
pub_type: 杂志文章
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doi:10.1046/j.1440-1711.2001.01008.x
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journal_title:Immunology and cell biology
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journal_title:Immunology and cell biology
pub_type: 杂志文章
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journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.2015.13
更新日期:2015-08-01 00:00:00
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journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.1992.51
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journal_title:Immunology and cell biology
pub_type: 杂志文章
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journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.2009.118
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journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.2014.97
更新日期:2015-03-01 00:00:00
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journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1046/j.1440-1711.2002.01125.x
更新日期:2002-12-01 00:00:00
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journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1111/imcb.1026
更新日期:2018-02-01 00:00:00
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journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1711.2000.00921.x
更新日期:2000-08-01 00:00:00
abstract::Many specific antiviral and antitumour immune responses have been attributed to the protective effects of antigen-specific CD8+ cytotoxic T lymphocytes (CTL). Recognition of virus infected or tumour cells by CTL requires presentation of at least one peptide epitope from a virus or tumour-specific antigen by the releva...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1046/j.1440-1711.2003.01130.x
更新日期:2003-02-01 00:00:00
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journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1038/icb.2017.22
更新日期:2017-08-01 00:00:00
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journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1111/j.0818-9641.2004.01247.x
更新日期:2004-08-01 00:00:00
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journal_title:Immunology and cell biology
pub_type: 杂志文章
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更新日期:1997-02-01 00:00:00
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pub_type: 杂志文章,评审
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journal_title:Immunology and cell biology
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pub_type: 杂志文章
doi:10.1046/j.1440-1711.2002.01109.x
更新日期:2002-10-01 00:00:00
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journal_title:Immunology and cell biology
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doi:10.1111/j.1440-1711.2004.01216.x
更新日期:2004-02-01 00:00:00
abstract::Arginase-1 (Arg-1)-expressing M2-like macrophages are associated with Th2-skewed immune responses, allergic airway pathology, ectopic B16 melanoma cancer growth in murine models, and can be induced by Oncostatin M (OSM) transient overexpression in vivo. Here, we compare OSM to the gp130-cytokine IL-6 in mediating macr...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1111/imcb.1035
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abstract::The Kunjin replicon was used to express a polytope that consisted of seven hepatitis C virus cytotoxic T lymphocyte epitopes and one influenza cytotoxic T lymphocyte epitope for vaccination studies. The self-replicating nature of, and expression from, the ribonucleic acid was confirmed in vitro. Initial vaccinations w...
journal_title:Immunology and cell biology
pub_type: 杂志文章
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更新日期:2003-02-01 00:00:00
abstract::The present report provides the first extensive characterization of the OT-I TCR transgenic line, which produces MHC class I-restricted, ovalbumin-specific, CD8+ T cells (OT-I cells). These cells are shown to be positively selected in vivo in H-2b C57BL/6 mice and in bm5 mice, which express the Kbm5 mutant molecule. I...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1046/j.1440-1711.2000.00889.x
更新日期:2000-04-01 00:00:00
abstract::Ex vivo mammary explant systems are an excellent model to study interactions between epithelium and stromal cell types because they contain physiologically relevant heterotypic interactions in the background of genetically diverse patients. The intact human mammary tissue, termed patient-derived explant (PDE), can be ...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1111/imcb.12381
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journal_title:Immunology and cell biology
pub_type: 杂志文章
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更新日期:2019-09-01 00:00:00
abstract::Rats intestinally immunized with whole killed non-typable Haemophilus influenzae clear this organism from the lungs faster than non-immunized rats. This study investigated the role of antibody and phagocytes in the clearance mechanism. First, dose-response experiments demonstrated that while lowering the dose of non-t...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.1995.42
更新日期:1995-06-01 00:00:00
abstract::Activin A, a member of the transforming growth factor-β superfamily, is a critical early mediator of acute inflammation. Activin A release coincides with the release of tumour necrosis factor-α (TNF-α) in models of lipopolysaccharide (LPS)-induced inflammation. The source of circulating activin A during acute inflamma...
journal_title:Immunology and cell biology
pub_type: 杂志文章
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更新日期:2011-11-01 00:00:00