Artificial antigen-presenting cells as a tool to exploit the immune `synapse'

Prakken, Berent J.; Wauben, Marca H. M.; Genini, Davide; Samodal, Rodrigo; Barnett, Joellen; Mendivil, Alberto; Leoni, Lorenzo M.; Albani, Salvatore

doi:10.1038/82231

Cited by 118 publications

(104 citation statements)

References 23 publications

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“…This preparation is a modification from our published method (22). Briefly, phosphatidylcholine and cholesterol (Sigma) are combined in a glass tube at a molar ratio of 7:2.…”

Section: Preparation Of Artificial Antigen-presenting Cells (Aapcs)mentioning

confidence: 99%

Epitope-specific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis

Prakken

Samodal

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Modulation of epitope-specific immune responses would represent a major addition to available therapeutic options for many autoimmune diseases. The objective of this work was to induce immune deviation by mucosal peptide-specific immunotherapy in rheumatoid arthritis (RA) patients, and to dissect the related immunological mechanisms by using a technology for the detection of low-affinity class II-restricted peptide-specific T cells. A group of patients with early RA was treated for 6 months orally with dnaJP1, a peptide that induces proinflammatory T cell responses in naive RA patients. Immunological analysis at initial, intermediate and end treatment points showed an intriguing change from proinflammatory to regulatory T cell function. In fact, dnaJP1-induced T cell production of IL-4 and IL-10 increased significantly when initial and end treatment points were compared, whereas dnaJP1-induced T cell proliferation and production of IL-2, IFN-␥, and tumor necrosis factor-␣ decreased significantly. The total number of dnaJP1-specific cells did not change over time, whereas expression of foxP3 by CD4 ؉ CD25 bright cells increased, suggesting that the treatment affected regulatory T cell function. Thus, rather than clonal deletion, the observed change in immune reactivity to dnaJP1 was the outcome of treatment-induced emergence of T cells with a different functional phenotype. This study contributes to our knowledge of mechanisms and tools needed for antigen-specific immune modulation in humans, thus laying the foundation for exploitation of this approach for therapeutic purposes.

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“…This preparation is a modification from our published method (22). Briefly, phosphatidylcholine and cholesterol (Sigma) are combined in a glass tube at a molar ratio of 7:2.…”

Section: Preparation Of Artificial Antigen-presenting Cells (Aapcs)mentioning

confidence: 99%

Epitope-specific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis

Prakken

Samodal

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

202

157

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“…9,10 However, expansion of CTLs is difficult due to the limited availability of donor-derived DCs. To date, several reports indicate effective stimulation of T cells by HLA/peptide ligands expressed on artificial antigenpresenting constructs (aAPCs) such as liposomes 11,12 or microbeads. [13][14][15][16] We developed aAPCs that can be manufactured under good manufacturing practice conditions and used to expand mHag-specific CTLs for adoptive immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Artificial antigen-presenting constructs efficiently stimulate minor histocompatibility antigen–specific cytotoxic T lymphocytes

Oosten

Blokland

Halteren

et al. 2004

Blood

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Cytotoxic T lymphocytes (CTLs) specific for hematopoietic-restricted minor histocompatibility antigens (mHags) are important reagents for adoptive immunotherapy of relapsed leukemia after allogeneic stem cell transplantation. However, expansion of these CTLs to therapeutic numbers is often hampered by the limited supply of antigen-presenting cells (APCs). Therefore, we evaluated whether cell-sized latex beads coated with HLA/mHag complexes HLA-A2/HA-1 or HLA-A2/HA-2 and recombinant CD80 and CD54 molecules can replace professional APCs. The artificial antigen-presenting constructs (aAPCs) effectively stimulated HA-1-and HA-2-specific CTL clones as shown by ligand-specific expansion, cytokine production, and maintenance of cytotoxic activity, without alteration of CTL phenotype. Furthermore, HA-1-specific polyclonal CTL lines were enriched as effi- IntroductionThe successful application of donor lymphocyte infusions for the treatment of relapsed leukemia after allogeneic stem cell transplantation illustrates the feasibility of adoptive immunotherapy of hematologic malignancies. 1 To minimize graft-versus-host disease, we earlier proposed the use of minor histocompatibility antigens (mHags) HA-1 and HA-2 as immunotherapeutic reagents. 2 HA-1 and HA-2 display hematopoietic-restricted tissue distribution and relevant expression on leukemic cells and their progenitors. [3][4][5][6] Moreover, cytotoxic T lymphocytes (CTLs) directed against these mHags do not cause graft-versus-host disease in an ex vivo skin explant model, 7 and coincide with complete remission of relapsed leukemia and multiple myeloma after HLA-matched HA-1-or HA-2-mismatched donor lymphocyte infusions. 8 HA-1-and HA-2-specific CTLs can be generated in vitro using peptide-pulsed or mHag-transduced autologous dendritic cells (DCs) as antigen-presenting cells (APCs). 9,10 However, expansion of CTLs is difficult due to the limited availability of donor-derived DCs. To date, several reports indicate effective stimulation of T cells by HLA/peptide ligands expressed on artificial antigenpresenting constructs (aAPCs) such as liposomes 11,12 or microbeads. [13][14][15][16] We developed aAPCs that can be manufactured under good manufacturing practice conditions and used to expand mHag-specific CTLs for adoptive immunotherapy. Hereto, cell-sized latex microbeads coated with HLA-A2/HA-1 or HLA-A2/HA-2 complexes, CD80, and CD54 were investigated for their potential to efficiently stimulate HA-1-and HA-2-specific CTL clones and lines while keeping their antigenspecific cytolytic properties. Study design mHag-specific CTL clones and polyclonal CTL lines, CD4 ؉ T helper cells, and DCsIn vivo and in vitro generation of mHag-specific CTL clones, polyclonal CTL lines, and DCs is documented in detail elsewhere. 9,17 CD4 ϩ T-helper cells (CD4 ϩ Th cells) were generated by culturing peripheral blood mononuclear cells (PBMCs) for 14 days in Iscove modified Dulbecco medium (IMDM) containing 10% pooled human serum (HS) and 0.5% standard Dutch diphtheria/pertussis/tetanus/po...

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“…The bead-based systems also have some drawbacks, including high cost of the beads, the labor-intensive process of removing the beads from the culture before infusion, and the inability of these beads to expand CD8 + T cells (21)(22)(23)(24). The artificial liposomes and exsomes show some potential for T-cell expansion, but the high cost, long-time procedure and biosafety should be considered for clinical therapy (25,26).…”

Section: Discussionmentioning

confidence: 99%

Establishment and Characterization of a Cell Based Artificial Antigen-Presenting Cell for Expansion and Activation of CD8+ T Cells Ex Vivo

et al. 2008

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Artificial antigen-presenting cells as a tool to exploit the immune `synapse'

Cited by 118 publications

References 23 publications

Epitope-specific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis

Epitope-specific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis

Artificial antigen-presenting constructs efficiently stimulate minor histocompatibility antigen–specific cytotoxic T lymphocytes

Establishment and Characterization of a Cell Based Artificial Antigen-Presenting Cell for Expansion and Activation of CD8+ T Cells Ex Vivo

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