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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, Yuri; Ueki, Hideto; A, Ruhan; Sasajima, Akari; Tomono, Takumi; Ukawa, Masami; Yagi, Haruya; Sakuma, Shinji; Kitagawa, Koichi; Shirakawa, Toshiro.
Afiliación
  • Fujioka Y; Department of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, Kobe 650-0017, Japan.
  • Ueki H; Department of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, Kobe 650-0017, Japan.
  • A R; Department of Urology, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan.
  • Sasajima A; Department of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, Kobe 650-0017, Japan.
  • Tomono T; Department of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, Kobe 650-0017, Japan.
  • Ukawa M; Faculty of Pharmaceutical Sciences, Setsunan University, Osaka 573-0101, Japan.
  • Yagi H; Faculty of Pharmaceutical Sciences, Setsunan University, Osaka 573-0101, Japan.
  • Sakuma S; Faculty of Pharmaceutical Sciences, Setsunan University, Osaka 573-0101, Japan.
  • Kitagawa K; Faculty of Pharmaceutical Sciences, Setsunan University, Osaka 573-0101, Japan.
  • Shirakawa T; Department of Advanced Medical Science, Graduate School of Science, Technology and Innovation, Kobe University, Kobe 650-0017, Japan.
Int J Mol Sci ; 25(11)2024 May 30.
Article en En | MEDLINE | ID: mdl-38892182
ABSTRACT
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Presentación de Antígeno / Vacunas contra el Cáncer Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Dendríticas / Presentación de Antígeno / Vacunas contra el Cáncer Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza