scholarly journals Dendritic Cells Loaded With mRNA Encoding Full-length Tumor Antigens Prime CD4+ and CD8+ T Cells in Melanoma Patients

2012 ◽  
Vol 20 (5) ◽  
pp. 1063-1074 ◽  
Author(s):  
An MT Van Nuffel ◽  
Daphné Benteyn ◽  
Sofie Wilgenhof ◽  
Lauranne Pierret ◽  
Jurgen Corthals ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Tumor Antigens ◽  
Full Length ◽  
Melanoma Patients

scholarly journals Vaccine Based on Dendritic Cells Electroporated with an Exogenous Ovalbumin Protein and Pulsed with Invariant Natural Killer T Cell Ligands Effectively Induces Antigen-Specific Antitumor Immunity

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 171
Author(s):  
Akihiro Watanabe ◽  
Kimihiro Yamashita ◽  
Mitsugu Fujita ◽  
Akira Arimoto ◽  
Masayasu Nishi ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Natural Killer ◽  
Cd8 T Cells ◽  
Antitumor Immunity ◽  
Tumor Antigens ◽  
Vaccine Strategy ◽  
Inkt Cells ◽  
Invariant Natural Killer ◽  
Natural Killer T

(1) Background: Cancer vaccines are administered to induce cytotoxic CD8+ T cells (CTLs) specific for tumor antigens. Invariant natural killer T (iNKT) cells, the specific T cells activated by α-galactosylceramide (α-GalCer), play important roles in this process as they are involved in both innate and adaptive immunity. We developed a new cancer vaccine strategy in which dendritic cells (DCs) were loaded with an exogenous ovalbumin (OVA) protein by electroporation (EP) and pulsed with α-GalCer. (2) Methods: We generated bone marrow-derived DCs from C57BL/6 mice, loaded full-length ovalbumin proteins to the DCs by EP, and pulsed them with α-GalCer (OVA-EP-galDCs). The OVA-EP-galDCs were intravenously administered to C57BL/6 mice as a vaccine. We then investigated subsequent immune responses, such as the induction of iNKT cells, NK cells, intrinsic DCs, and OVA-specific CD8+ T cells, including tissue-resident memory T (TRM) cells. (3) Results: The OVA-EP-galDC vaccine efficiently rejected subcutaneous tumors in a manner primarily dependent on CD8+ T cells. In addition to the OVA-specific CD8+ T cells both in early and late phases, we observed the induction of antigen-specific TRM cells in the skin. (4) Conclusions: The OVA-EP-galDC vaccine efficiently induced antigen-specific antitumor immunity, which was sustained over time, as shown by the TRM cells.

scholarly journals 612 Human CLEC9A antibodies deliver NY-ESO-1 antigen to CD141+ dendritic cells to activate naïve and memory NY-ESO-1-specific CD8+ T cells

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A648-A648
Author(s):  
Kelly-Anne Masterman ◽  
Oscar Haigh ◽  
Kirsteen Tullett ◽  
Ingrid Leal-Rojas ◽  
Carina Walpole ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Ethics Committee ◽  
Cross Presentation ◽  
Cell Responses ◽  
Melanoma Patients

BackgroundDendritic cells (DC) 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+ DC, the human cDC1 equivalent. CD141+ DC 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 to human CD141+ DC. 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 to a vaccine comprised of a human DEC-205-NY-ESO-1 antibody that targets all human DC.MethodsHuman 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 melanoma patients was assessed by IFNγ production following incubation of CD141+ DC 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, TNF and CD107a and by lysis of target tumor cells.ResultsCLEC9A-NY-ESO-1 Ab were effective at mediating delivery and cross-presentation of multiple NY-ESO-1 epitopes by CD141+ DC 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 melanoma patients. 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.ConclusionsThese data advocate human CLEC9A-NY-ESO-1 antibody as an attractive strategy for specific targeting of CD141+ DC to enhance tumour immunogenicity in NY-ESO-1-expressing malignancies.Ethics ApprovalWritten informed consent was obtained for human sample acquisition in line with standards established by the Declaration of Helsinki. Study approval was granted by the Mater Human Research Ethics Committee (HREC13/MHS/83 and HREC13/MHS/86) and The U.S. Army Medical Research and Materiel Command (USAMRMC) Office of Research Protections, Human Research Protection Office (HRPO; A-18738.1, A-18738.2, A-18738.3). All animal experiments were approved by the University of Queensland Animal Ethics Committee and conducted in accordance with the Australian Code for the Care and Use of Animals for Scientific Purposes in addition to the laws of the United States and regulations of the Department of Agriculture.

Epitope and HLA-type independent monitoring of antigen-specific T-cells after treatment with dendritic cells presenting full-length tumor antigens

2012 ◽  
Vol 377 (1-2) ◽  
pp. 23-36 ◽  
Author(s):  
An M.T. Van Nuffel ◽  
Sandra Tuyaerts ◽  
Daphné Benteyn ◽  
Sofie Wilgenhof ◽  
Jurgen Corthals ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Tumor Antigens ◽  
Full Length ◽  
Hla Type

scholarly journals Vaccination with mRNA-Electroporated Dendritic Cells Induces Robust Tumor Antigen-Specific CD4+ and CD8+ T Cells Responses in Stage III and IV Melanoma Patients

2012 ◽  
Vol 18 (19) ◽  
pp. 5460-5470 ◽  
Author(s):  
Erik H. J. G. Aarntzen ◽  
Gerty Schreibelt ◽  
Kalijn Bol ◽  
W. Joost Lesterhuis ◽  
Alexandra J. Croockewit ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Tumor Antigen ◽  
Stage Iii ◽  
Melanoma Patients

scholarly journals Cross-Priming of Naive Cd8 T Cells against Melanoma Antigens Using Dendritic Cells Loaded with Killed Allogeneic Melanoma Cells

2000 ◽  
Vol 192 (11) ◽  
pp. 1535-1544 ◽  
Author(s):  
Frederic Berard ◽  
Patrick Blanco ◽  
Jean Davoust ◽  
Eve-Marie Neidhart-Berard ◽  
Mahyar Nouri-Shirazi ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Tumor Antigens ◽  
Cytotoxic T Lymphocyte ◽  
Melanoma Cells ◽  
Autologous Tumor ◽  
Multiple Tumor ◽  
Melanoma Antigens

The goal of tumor immunotherapy is to elicit immune responses against autologous tumors. It would be highly desirable that such responses include multiple T cell clones against multiple tumor antigens. This could be obtained using the antigen presenting capacity of dendritic cells (DCs) and cross-priming. That is, one could load the DC with tumor lines of any human histocompatibility leukocyte antigen (HLA) type to elicit T cell responses against the autologous tumor. In this study, we show that human DCs derived from monocytes and loaded with killed melanoma cells prime naive CD45RA+CD27+CD8+ T cells against the four shared melanoma antigens: MAGE-3, gp100, tyrosinase, and MART-1. HLA-A201+ naive T cells primed by DCs loaded with HLA-A201− melanoma cells are able to kill several HLA-A201+ melanoma targets. Cytotoxic T lymphocyte priming towards melanoma antigens is also obtained with cells from metastatic melanoma patients. This demonstration of cross-priming against shared tumor antigens builds the basis for using allogeneic tumor cell lines to deliver tumor antigens to DCs for vaccination protocols.

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