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Facilitating the presentation of antigen peptides on dendritic cells for cancer immunotherapy using a polymer-based synthetic receptor.

ABSTRACT: The introduction of proteins into dendritic cells (DCs) ex vivo is a critical step for the DC-based immunotherapy of cancer. Here, we developed a biotin-modified polymer with multiple hydrophobic membrane anchors for cells that functions as a synthetic receptor for an antigen protein, ovalbumin (OVA), to introduce it efficiently into DCs compared with the conventional pulsing method. Our method showed significant advantages, including the rapid incorporation of OVA and the activation of antigen-specific T cells in a MHC-restricted manner. When mice were immunized by DCs treated with our method, tumor growth was completely suppressed, indicating that our method can be used to prepare adjuvant DCs.

SUBMITTER: Li C

PROVIDER: S-EPMC6072308 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Facilitating the presentation of antigen peptides on dendritic cells for cancer immunotherapy using a polymer-based synthetic receptor.

Li Cuicui C Takeo Masafumi M Matsuda Masayoshi M Nagai Hiroko H Xizheng Sun S Hatanaka Wataru W Kishimura Akihiro A Inoue Hiroyuki H Tani Kenzaburo K Mori Takeshi T Katayama Yoshiki Y

MedChemComm 20170512 6

The introduction of proteins into dendritic cells (DCs) <i>ex vivo</i> is a critical step for the DC-based immunotherapy of cancer. Here, we developed a biotin-modified polymer with multiple hydrophobic membrane anchors for cells that functions as a synthetic receptor for an antigen protein, ovalbumin (OVA), to introduce it efficiently into DCs compared with the conventional pulsing method. Our method showed significant advantages, including the rapid incorporation of OVA and the activation of a ...[more]

PMID: 30108830

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Inhibition of antigen presentation during AAV gene therapy using virus peptides.

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| S-EPMC5886241 | biostudies-literature

Self-adjuvanting nanoemulsion targeting dendritic cell receptor Clec9A enables antigen-specific immunotherapy.

Project description:Non-antigen-specific stimulatory cancer immunotherapies are commonly complicated by off-target effects. Antigen-specific immunotherapy, combining viral tumor antigen or personalized neoepitopes with immune targeting, offers a solution. However, the lack of flexible systems targeting tumor antigens to cross-presenting dendritic cells (DCs) limits clinical development. Although antigen-anti-Clec9A mAb conjugates target cross-presenting DCs, adjuvant must be codelivered for cytotoxic T lymphocyte (CTL) induction. We functionalized tailored nanoemulsions encapsulating tumor antigens to target Clec9A (Clec9A-TNE). Clec9A-TNE encapsulating OVA antigen targeted and activated cross-presenting DCs without additional adjuvant, promoting antigen-specific CD4+ and CD8+ T cell proliferation and CTL and antibody responses. OVA-Clec9A-TNE-induced DC activation required CD4 and CD8 epitopes, CD40, and IFN-?. Clec9A-TNE encapsulating HPV E6/E7 significantly suppressed HPV-associated tumor growth, while E6/E7-CpG did not. Clec9A-TNE loaded with pooled B16-F10 melanoma neoepitopes induced epitope-specific CD4+ and CD8+ T cell responses, permitting selection of immunogenic neoepitopes. Clec9A-TNE encapsulating 6 neoepitopes significantly suppressed B16-F10 melanoma growth in a CD4+ T cell-dependent manner. Thus, cross-presenting DCs targeted with antigen-Clec9A-TNE stimulate therapeutically effective tumor-specific immunity, dependent on T cell help.

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Manipulating antigen presentation for antigen-specific immunotherapy of autoimmune diseases.

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First characterization of Plasmodium vivax liver stage antigen (PvLSA) using synthetic peptides.

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| S-EPMC1948949 | biostudies-literature

Autonomous phagosomal degradation and antigen presentation in dendritic cells.

Project description:Phagocytosis plays a critical role in both innate and adaptive immunity. Phagosomal fusion with late endosomes and lysosomes enhances proteolysis, causing degradation of the phagocytic content. Increased degradation participates in both innate protection against pathogens and the production of antigenic peptides for presentation to T lymphocytes during adaptive immune responses. Specific ligands present in the phagosomal cargo influence the rate of phagosome fusion with lysosomes, thereby modulating both antigen degradation and presentation. Using a combination of cell sorting techniques and single phagosome flow cytometry-based analysis, we found that opsonization with IgG accelerates antigen degradation within individual IgG-containing phagosomes, but not in other phagosomes present in the same cell and devoid of IgG. Likewise, IgG opsonization enhances antigen presentation to CD4(+) T lymphocytes only when antigen and IgG are present within the same phagosome, whereas cells containing phagosomes with either antigen or IgG alone failed to present antigen efficiently. Therefore, individual phagosomes behave autonomously, in terms of both cargo degradation and antigen presentation to CD4(+) T cells. Phagosomal autonomy could serve as a basis for the intracellular discrimination between self and nonself antigens, resulting in the preferential presentation of peptides derived from opsonized, nonself antigens.

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