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

Watanabe, Akihiro; Yamashita, Kimihiro; Fujita, Mitsugu; Arimoto, Akira; Nishi, Masayasu; Takamura, Shiki; Saito, Masafumi; Yamada, Katsushi; Agawa, Kyosuke; Mukoyama, Tomosuke; Ando, Masashi; Kanaji, Shingo; Matsuda, Takeru; Oshikiri, Taro; Kakeji, Yoshihiro

doi:10.3390/cancers14010171

Cited by 3 publications

(1 citation statement)

References 54 publications

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“…In addition, the mixture of EL4 lysate with VP-R8 did not affect cell viability after pulsation. Electroporation is one of the efficient methods to transduce proteins into dendritic cells to induce dendritic cell-based vaccines, but preserving cell viability after transduction is challenging [ 22 ]. Our results suggested that VP-R8 is a safer and more efficient modality to deliver tumor antigens into dendritic cells than conventional electroporation.…”

Section: Discussionmentioning

confidence: 99%

The Improved Antigen Uptake and Presentation of Dendritic Cells Using Cell-Penetrating D-octaarginine-Linked PNVA-co-AA as a Novel Dendritic Cell-Based Vaccine

Fujioka,

Ueki,

et al. 2024

IJMS

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Cancer immunotherapy using antigen-pulsed dendritic cells can induce strong cellular immune responses by priming cytotoxic T lymphocytes. In this study, we pulsed tumor cell lysates with VP-R8, a cell-penetrating D-octaarginine-linked co-polymer of N-vinylacetamide and acrylic acid (PNVA-co-AA), into the DC2.4 murine dendritic cell line to improve antigen uptake and then determined the anti-tumor effect in tumor-bearing mice. DC2.4 cells were pulsed with the cell lysate of EL4, a murine lymphoma cell line, and VP-R8 to generate the DC2.4 vaccine. For the in vivo study, DC2.4 cells pulsed with EL4 lysate and VP-R8 were subcutaneously injected into the inguinal lymph node to investigate the anti-tumor effect against EL4 and EL4-specific T cell immune responses. VP-R8 significantly improved antigen uptake into DC2.4 compared to conventional keyhole limpet hemocyanin (p < 0.05). The expression of MHC class I, MHC class II, and CD86 in DC2.4 cells significantly increased after pulsing tumor lysates with VP-R8 compared to other treatments (p < 0.05). The intra-lymph node injection of DC2.4 pulsed with both VP-R8 and EL4 lysate significantly decreased tumor growth compared to DC2.4 pulsed with KLH and lysates (p < 0.05) and induced tumor-infiltrating CD8T cells. The DC2.4 vaccine also remarkably increased the population of IFN-gamma-producing T cells and CTL activity against EL4 cells. In conclusion, we demonstrated that VP-R8 markedly enhances the efficiency of dendritic cell-based vaccines in priming robust anti-tumor immunity, suggesting its potential as a beneficial additive for dendritic cell-based immunotherapy.

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Section: Discussionmentioning

confidence: 99%

The Improved Antigen Uptake and Presentation of Dendritic Cells Using Cell-Penetrating D-octaarginine-Linked PNVA-co-AA as a Novel Dendritic Cell-Based Vaccine

Fujioka,

Ueki,

et al. 2024

IJMS

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The effect of buffer concentration on the dynamic/equilibrium surface tension of bovine serum albumin solution

Hussain

Hung

Tseng

et al. 2023

Journal of Molecular Liquids

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Recruiting Natural Killer T Cells to Improve Vaccination: Lessons from Preclinical and Clinical Studies

2024

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The capacity of type I natural killer T (NKT) cells to provide stimulatory signals to antigen-presenting cells has prompted preclinical research into the use of agonists as immune adjuvants, with much of this work focussed on stimulating T cell responses to cancer. In attempting to evaluate this approach in the clinic, our recent dendritic-cell based study failed to show an advantage to adding an agonist to the vaccine. Here we present potential limitations of the study, and suggest why other simpler strategies may be more effective. These include strategies to target antigen-presenting cells in the host, either through promoting efficient transfer from injected cell lines, facilitating uptake of antigen and agonist as injected conjugates, or encapsulating the components into injected nanovectors. While the vaccine landscape has changed with the rapid uptake of mRNA vaccines, we suggest that there is still a role for recruiting NKT cells in altering T cell differentiation programmes, notably the induction of resident memory T cells.

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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

Cited by 3 publications

References 54 publications

The Improved Antigen Uptake and Presentation of Dendritic Cells Using Cell-Penetrating D-octaarginine-Linked PNVA-co-AA as a Novel Dendritic Cell-Based Vaccine

The Improved Antigen Uptake and Presentation of Dendritic Cells Using Cell-Penetrating D-octaarginine-Linked PNVA-co-AA as a Novel Dendritic Cell-Based Vaccine

The effect of buffer concentration on the dynamic/equilibrium surface tension of bovine serum albumin solution

Recruiting Natural Killer T Cells to Improve Vaccination: Lessons from Preclinical and Clinical Studies

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