Dataset Information

Cowpea Mosaic Virus (CPMV)-Based Cancer Testis Antigen NY-ESO-1 Vaccine Elicits an Antigen-Specific Cytotoxic T Cell Response.

ABSTRACT: Cancer vaccines are promising adjuvant immunotherapies that can stimulate the immune system to recognize tumor-associated antigens and eliminate the residual or recurring disease. The aberrant and restricted expression of highly immunogenic cancer testis antigen NY-ESO-1 in several malignancies, including triple-negative breast cancer, melanoma, myelomas, and ovarian cancer, makes NY-ESO-1 an attractive antigenic target for cancer vaccines. This study describes a NY-ESO-1 vaccine based on a bio-inspired nanomaterial platform technology, specifically a plant virus nanoparticle. The 30 nm icosahedral plant virus cowpea mosaic virus (CPMV) displaying multiple copies of human HLA-A2 restricted peptide antigen NY-ESO-1_157-165 exhibited enhanced uptake and activation of antigen-presenting cells and stimulated a potent CD8⁺ T cell response in transgenic human HLA-A2 expressing mice. CD8⁺ T cells from immunized mice exhibited antigen-specific proliferation and cancer cell cytotoxicity, highlighting the potential application of a CPMV-NY-ESO-1 vaccine against NY-ESO-1⁺ malignancies.

SUBMITTER: Patel BK

PROVIDER: S-EPMC8340627 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cowpea Mosaic Virus (CPMV)-Based Cancer Testis Antigen NY-ESO-1 Vaccine Elicits an Antigen-Specific Cytotoxic T Cell Response.

Patel Bindi K BK Wang Chao C Lorens Braulio B Levine Alan D AD Steinmetz Nicole F NF Shukla Sourabh S

ACS applied bio materials 20200625 7

Cancer vaccines are promising adjuvant immunotherapies that can stimulate the immune system to recognize tumor-associated antigens and eliminate the residual or recurring disease. The aberrant and restricted expression of highly immunogenic cancer testis antigen NY-ESO-1 in several malignancies, including triple-negative breast cancer, melanoma, myelomas, and ovarian cancer, makes NY-ESO-1 an attractive antigenic target for cancer vaccines. This study describes a NY-ESO-1 vaccine based on a bio- ...[more]

PMID: 34368641

Similar Datasets

Project description: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.

Dataset Information

Cowpea Mosaic Virus (CPMV)-Based Cancer Testis Antigen NY-ESO-1 Vaccine Elicits an Antigen-Specific Cytotoxic T Cell Response.

Publications

Cowpea Mosaic Virus (CPMV)-Based Cancer Testis Antigen NY-ESO-1 Vaccine Elicits an Antigen-Specific Cytotoxic T Cell Response.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets