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

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), int...

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Bibliographic Details
Published in:	International journal of molecular sciences Vol. 25; no. 11; p. 5997
Main Authors:	Fujioka, Yuri, Ueki, Hideto, A, Ruhan, Sasajima, Akari, Tomono, Takumi, Ukawa, Masami, Yagi, Haruya, Sakuma, Shinji, Kitagawa, Koichi, Shirakawa, Toshiro
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 01-06-2024 MDPI
Subjects:	Animals Antigen Presentation - immunology Antigens Cancer cancer immunotherapy Cancer therapies Cancer Vaccines - immunology Cell Line, Tumor Cell-Penetrating Peptides - chemistry cell-penetrating polymer Chemotherapy Cytokines Cytotoxicity dendritic cell vaccine Dendritic cells Dendritic Cells - immunology drug delivery system Executives Female Flow cytometry Health aspects Immune system Immunotherapy Lymphatic system Lymphocytes Lymphoma Mice Mice, Inbred C57BL Mortality Oligopeptides - chemistry Permeability Polymers Prognosis Radiation therapy Spleen T cells Tumors Vaccines Japan cell-penetrating polymer drug delivery system dendritic cell vaccine cancer immunotherapy
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Summary:	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 ( < 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 ( < 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 ( < 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms25115997