Micro- and Nanoengineering of the Cell Surface

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Recent Activity. The snippet could not be located in the article text. This may be because the snippet appears in a figure legend, contains special characters or spans different sections of the article. Nanomedicine Lond. Author manuscript; available in PMC Mar PMID: For reprint orders, please contact: moc. Copyright notice. The publisher's final edited version of this article is available at Nanomedicine Lond.

See other articles in PMC that cite the published article. Abstract Artificial antigen-presenting cells aAPCs have shown great initial promise for ex vivo activation of cytotoxic T cells. Keywords: anisotropy, artificial antigen-presenting cell, biomimetic, immunology, nanobiotechnology, nanoparticle, particle shape, polymer. Table 1 Key parameters of current- and future-generation artificial antigen-presenting cells and their biological rationale. Open in a separate window. Figure 1.

Micro- and Nanoengineering of the Cell Surface by Weian Zhao, Jeffrey M Karp

Figure 2. TCR: T-cell receptor. Signal 3: cytokine release One of the advantages of a biodegradable aAPC system compared with a nondegradable aAPC system is that the biodegradable system can be engineered to release soluble factors from within the aAPC in addition to presenting factors that are attached to the aAPC surface.

Nanoscale approaches to mimicking the organization of the IS Nanoscale surface patterning Most aAPC systems utilize uniform presentation of ligands on the surface, due to ease of fabrication and simplicity of design.

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Figure 3. Figure 4. Nanoscale biphasic Janus particles A The experimental setup used for generation of nanoscale biphasic Janus particles. Figure 5. A particle-supported lipid bilayer with the range of cargoes and surface ligands that can be encapsulated or presented on the surface of the particle DOPC: 1,2-dioleoyl-sn-glycerophosphocholine; DOPE: 1,2-dioleoyl-sn-glycerophosphoethanolamine; DPPC: 1,2-dipalmitoyl-sn- glycerophosphorylcholine; DPPE: 1,2-dipalmitoyl-sn-glycerophosphorylethanolamine; PE: Polyethylene.

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  6. Altered particle shape The use of nonspherical particles has generated increasing interest in recent years for biomedical applications. Methods to engineer polymeric aAPC shape Perhaps the simplest and most accessible method developed for generating nonspherical particles uses a film-stretching technique originally developed by Ho et al. Figure 6. Potential particle shapes of interest for artificial antigen-presenting cell development Diverse shapes can be made using a film-stretching method using A—H microparticles and I nanoparticles. Acellular artificial antigen-presenting cells Acellular artificial antigen-presenting cells aAPCs are micro- or nano-particle-based reductionist systems that mimic the biological cues given by activated biological antigen-presenting cells to T cells to direct T-cell fate and induce cellular immunity.

    Nanoengineering approaches for next-generation aAPCs Most current-generation aAPCs employ static isotropic presentation of protein signals, but advances in nanoengineering approaches may allow for better biomimicry through the addition of nanoscale features to microscale aAPCs, and may improve the potential of nanoparticle-based aAPCs. Engineering surface protein organization for increased biomimicry New techniques for the synthesis of patchy particles allows for fixed ligand organization that may be able to mimic the geometry and organization of the mature immunological synapse.

    Liposomes and particle-supported lipid bilayers can allow for surface presentation of organized nanoclusters prior to T-cell contact, and allow for the dynamic surface rearrangements seen in the biological setting. Modulation of particle shape to increase surface contact area Experiments with aAPC particle size have indicated that receptor occupancy over a large surface area of contact is a critical determinant for activation. Alterations in particle shape enable increased surface area for cell contact, allowing for nanoparticles with interfacial geometry similar to successful microparticulate systems, with improved in vivo performance due to easy access to draining lymph nodes, and suitability for intravenous injection.

    References Papers of special note have been highlighted as: of interest of considerable interest 1. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma.

    A listing of human tumor antigens recognized by T cells: March update.


    Cancer Immunol Immunother. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. Ex vivo induction and expansion of antigen-specific cytotoxic T cells by HLA-Ig-coated artificial antigen-presenting cells. Nat Med. Nat Biotechnol. A comprehensive platform for ex vivo T-cell expansion based on biodegradable polymeric artificial antigen-presenting cells. Mol Ther. An artificial antigen-presenting cell with paracrine delivery of IL-2 impacts the magnitude and direction of the T cell response. J Biol Chem.

    Demonstrated paracrine cytokine release from biodegradable artificial antigen-presenting cells with stable presentation of surface ligands. Mescher MF. Surface contact requirements for activation of cytotoxic T lymphocytes. J Immunol. Artificial cell surface constructs for studying receptor-ligand contributions to lymphocyte activation. J Immunol Methods.

    Nanoengineering 100TB HAMR Hard Drives with Professor Kyriakos Komvopoulos of Berkeley University

    Artificial antigen-presenting cells for use in adoptive immunotherapy. Cancer J. Nanoparticles target distinct dendritic cell populations according to their size. Eur J Immunol.

    Gilboa E. The makings of a tumor rejection antigen. CD28 delivers a costimulatory signal involved in antigen-specific IL-2 production by human T cells. The immunological synapse: a molecular machine controlling T cell activation. T cell receptor signaling precedes immunological synapse formation. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma A preliminary report.

    Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Induction and clonal expansion of tumor-specific cytotoxic T lymphocytes from renal cell carcinoma patients after stimulation with autologous dendritic cells loaded with tumor cells.

    Micro- and Nanoengineering of the Cell Surface

    Int J Cancer. Phenotypic analysis of antigen-specific T lymphocytes. Reversible HLA multimers streptamers for the isolation of human cytotoxic T lymphocytes functionally active against tumor- and virus-derived antigens.

    Polymeric materials for gene delivery and dna vaccination. Adv Mater. Rosenberg SA. Raising the bar: the curative potential of human cancer immunotherapy. Sci Transl Med. Cancer regression in patients after transfer of genetically engineered lymphocytes. Clustering of T cell ligands on artificial APC membranes influences T cell activation and protein kinase C theta translocation to the T cell plasma membrane. Demonstrates the utility and importance of protein signal preclustering in liposomal acellular artificial antigen-presenting cells.

    In vivo administration of artificial antigen-presenting cells activates low-avidity T cells for treatment of cancer. Cancer Res. Clin Immunol. A novel system of artificial antigen-presenting cells efficiently stimulates Flu peptide-specific cytotoxic T cells in vitro. Biochem Biophys Res Commun.

    Killer artificial antigen-presenting cells: a novel strategy to delete specific T cells. Ex vivo induction and expansion of natural killer T cells by CD1d1-Ig coated artificial antigen-presenting cells. Connecting the dots: artificial antigen-presenting cell-mediated modulation of natural killer T cells. J Interferon Cytokine Res. A novel system for simultaneous in vivo tracking and biological assessment of leukemia cells and ex vivo generated leukemia-reactive cytotoxic T cells. Antigen-specific blockade of T cells in vivo using dimeric MHC peptide. Tissue Antigens. Programmed death-1 ligand 1 interacts specifically with the B costimulatory molecule to inhibit T cell responses.

    Dynamic regulation of functionally distinct virus-specific T cells.

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    A stepwise protocol to coat aAPC beads prevents out-competition of anti-CD3 mAb and consequent experimental artefacts. Absorbable microparticulate cation exchanger for immunotherapeutic delivery. Surface modification of biodegradable polyesters with fatty acid conjugates for improved drug targeting. Pawar AB, Kretzschmar I.