Please use this identifier to cite or link to this item:
https://ahro.austin.org.au/austinjspui/handle/1/23917
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DC Field | Value | Language |
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dc.contributor.author | Masterman, Kelly-Anne | - |
dc.contributor.author | Haigh, Oscar L | - |
dc.contributor.author | Tullett, Kirsteen M | - |
dc.contributor.author | Leal-Rojas, Ingrid M | - |
dc.contributor.author | Walpole, Carina | - |
dc.contributor.author | Pearson, Frances E | - |
dc.contributor.author | Cebon, Jonathan S | - |
dc.contributor.author | Schmidt, Christopher | - |
dc.contributor.author | O'Brien, Liam | - |
dc.contributor.author | Rosendahl, Nikita | - |
dc.contributor.author | Daraj, Ghazal | - |
dc.contributor.author | Caminschi, Irina | - |
dc.contributor.author | Gschweng, Eric H | - |
dc.contributor.author | Hollis, Roger P | - |
dc.contributor.author | Kohn, Donald B | - |
dc.contributor.author | Lahoud, Mireille H | - |
dc.contributor.author | Radford, Kristen J | - |
dc.date | 2020-07 | - |
dc.date.accessioned | 2020-08-03T06:35:49Z | - |
dc.date.available | 2020-08-03T06:35:49Z | - |
dc.date.issued | 2020-07 | - |
dc.identifier.citation | Journal for Immunotherapy of Cancer 2020; 8(2): e000691 | en |
dc.identifier.uri | https://ahro.austin.org.au/austinjspui/handle/1/23917 | - |
dc.description.abstract | Dendritic cells (DCs) are crucial for the efficacy of cancer vaccines, but current vaccines do not harness the key cDC1 subtype required for effective CD8+ T-cell-mediated tumor immune responses. Vaccine immunogenicity could be enhanced by specific delivery of immunogenic tumor antigens to CD141+ DCs, the human cDC1 equivalent. CD141+ DCs exclusively express the C-type-lectin-like receptor CLEC9A, which is important for the regulation of CD8+ T cell responses. This study developed a new vaccine that harnesses a human anti-CLEC9A antibody to specifically deliver the immunogenic tumor antigen, NY-ESO-1 (New York esophageal squamous cell carcinoma 1), to human CD141+ DCs. The ability of the CLEC9A-NY-ESO-1 antibody to activate NY-ESO-1-specific naïve and memory CD8+ T cells was examined and compared with a vaccine comprised of a human DEC-205-NY-ESO-1 antibody that targets all human DCs. Human anti-CLEC9A, anti-DEC-205 and isotype control IgG4 antibodies were genetically fused to NY-ESO-1 polypeptide. Cross-presentation to NY-ESO-1-epitope-specific CD8+ T cells and reactivity of T cell responses in patients with melanoma were assessed by interferon γ (IFNγ) production following incubation of CD141+ DCs and patient peripheral blood mononuclear cells with targeting antibodies. Humanized mice containing human DC subsets and a repertoire of naïve NY-ESO-1-specific CD8+ T cells were used to investigate naïve T cell priming. T cell effector function was measured by expression of IFNγ, MIP-1β, tumor necrosis factor and CD107a and by lysis of target tumor cells. CLEC9A-NY-ESO-1 antibodies (Abs) were effective at mediating delivery and cross-presentation of multiple NY-ESO-1 epitopes by CD141+ DCs for activation of NY-ESO-1-specific CD8+ T cells. When benchmarked to NY-ESO-1 conjugated to an untargeted control antibody or to anti-human DEC-205, CLEC9A-NY-ESO-1 was superior at ex vivo reactivation of NY-ESO-1-specific T cell responses in patients with melanoma. Moreover, CLEC9A-NY-ESO-1 induced priming of naïve NY-ESO-1-specific CD8+ T cells with polyclonal effector function and potent tumor killing capacity in vitro. These data advocate human CLEC9A-NY-ESO-1 Ab as an attractive strategy for specific targeting of CD141+ DCs to enhance tumor immunogenicity in NY-ESO-1-expressing malignancies. | en |
dc.language.iso | eng | |
dc.subject | dendritic cells | en |
dc.subject | immunogenicity, vaccine | en |
dc.subject | immunotherapy | en |
dc.subject | melanoma | en |
dc.title | Human CLEC9A antibodies deliver NY-ESO-1 antigen to CD141+ dendritic cells to activate naïve and memory NY-ESO-1-specific CD8+ T cells. | en |
dc.type | Journal Article | en |
dc.identifier.journaltitle | Journal for Immunotherapy of Cancer | en |
dc.identifier.affiliation | Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia | en |
dc.identifier.affiliation | Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, USA | en |
dc.identifier.affiliation | Olivia Newton-John Cancer Research Institute | en |
dc.identifier.affiliation | Mater Research Institute, University of Queensland, Woolloongabba, Queensland, Australia | en |
dc.identifier.affiliation | Clinical Haematology | en |
dc.identifier.affiliation | Medical Oncology | en |
dc.identifier.doi | 10.1136/jitc-2020-000691 | en |
dc.type.content | Text | en |
dc.identifier.orcid | 0000-0001-6512-6323 | en |
dc.identifier.pubmedid | 32737142 | |
dc.type.austin | Journal Article | |
local.name.researcher | Cebon, Jonathan S | |
item.openairetype | Journal Article | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | none | - |
item.fulltext | No Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.languageiso639-1 | en | - |
crisitem.author.dept | Olivia Newton-John Cancer Research Institute | - |
Appears in Collections: | Journal articles |
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