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A Comprehensive Platform for Ex Vivo T-cell Expansion Based on Biodegradable Polymeric Artificial Antigen-presenting Cells
Open accessAbstract
Efficient T-cell stimulation and proliferation in response to specific antigens is a goal of immunotherapy against infectious disease and cancer. Manipulation of this response can be accomplished by adoptive immunotherapy involving the infusion of antigen-specific T-cell populations expanded ex vivo with antigen presenting cells. We mimicked physiological antigen presentation on a biodegradable microparticle constructed from poly(lactide-co-glycolide) (PLGA), a polymer system whose safety has been established for use in humans. These particles present a high density of adaptor elements for attaching both recognition ligands and co-stimulatory ligands to a biodegradable core encapsulating the cytokine interleukin-2 (IL-2). We demonstrate the utility of this system in efficient polyclonal and antigen-specific T-cell stimulation and expansion, showing that sustained release of IL-2 in the vicinity of T-cell contacts dramatically improves the stimulatory capacity of these acellular systems, as compared to the effect of exogenous addition of cytokine. This results in a 45-fold enhancement in T-cell expansion. In addition, this mode of antigen presentation skews the expansion toward the CD8(+) T-cell phenotype. This comprehensive acellular platform, capable of delivering recognition, co-stimulatory, and cytokine signals, represents a promising new technology for artificial antigen presentation.
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Cites
Polymers for the sustained release of proteins and other macromolecules
LANGER, R., & FOLKMAN, J. (1976) · Nature · doi:10.1038/263797a0 · Cited by 1,182
Alexis, F. (2005) · Polymer International · doi:10.1002/pi.1697 · Cited by 443
Research works printed but not linked: 44
- Papadopoulos, 1994, Infusions of donor leukocytes to treat Epstein-Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation, N Engl J Med, 330, 1185, 10.1056/NEJM199404283301703 · DOI · Paper page
- Savoldo, 2000, The use of cytotoxic t cells for the prevention and treatment of epstein-barr virus induced lymphoma in transplant recipients, Leuk Lymphoma, 39, 455, 10.3109/10428190009113376 · DOI
- Hori, 2003, Control of autoimmunity by naturally arising regulatory CD4+ T cells, Adv Immunol, 81, 331, 10.1016/S0065-2776(03)81008-8 · DOI · Paper page
- Karim, 2004, Alloantigen-induced CD25+CD4+ regulatory T cells can develop in vivo from CD25-CD4+ precursors in a thymus-independent process, J Immunol, 172, 923, 10.4049/jimmunol.172.2.923 · DOI · Paper page
- Dudley, 2003, Adoptive-cell-transfer therapy for the treatment of patients with cancer, Nat Rev Cancer, 3, 666, 10.1038/nrc1167 · DOI · Paper page
- Riddell, 2002, T-cell therapy of leukemia, Cancer Control, 9, 114, 10.1177/107327480200900204 · DOI
- Yee, 2002, Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells, Proc Natl Acad Sci USA, 99, 16168, 10.1073/pnas.242600099 · DOI · Paper page
- Oelke, 2003, Ex vivo induction and expansion of antigen-specific cytotoxic T cells by HLA-Ig-coated artificial antigen-presenting cells, Nat Med, 9, 619, 10.1038/nm869 · DOI · Paper page
- Kim, 2004, The ABCs of artificial antigen presentation, Nat Biotechnol, 22, 403, 10.1038/nbt955 · DOI · Paper page
- Hirano, 2006, Efficient presentation of naturally processed HLA class I peptides by artificial antigen-presenting cells for the generation of effective antitumor responses, Clin Cancer Res, 12, 2967, 10.1158/1078-0432.CCR-05-2791 · DOI
- Maus, 2002, Ex vivo expansion of polyclonal and antigen-specific cytotoxic T lymphocytes by artificial APCs expressing ligands for the T-cell receptor, CD28 and 4-1BB, Nat Biotechnol, 20, 143, 10.1038/nbt0202-143 · DOI · Paper page
- Mitchell, 2002, Phase I trial of adoptive immunotherapy with cytolytic T lymphocytes immunized against a tyrosinase epitope, J Clin Oncol, 20, 1075, 10.1200/JCO.20.4.1075 · doi:10.1200/jco.20.4.1075
- Jackson, 1992, Empty and peptide-containing conformers of class I major histocompatibility complex molecules expressed in Drosophila melanogaster cells, Proc Natl Acad Sci USA, 89, 12117, 10.1073/pnas.89.24.12117 · DOI
- Sun, 1996, Dual function of Drosophila cells as APCs for naive CD8+ T cells: implications for tumor immunotherapy, Immunity, 4, 555, 10.1016/S1074-7613(00)80482-3 · DOI
- Latouche, 2000, Induction of human cytotoxic T lymphocytes by artificial antigen-presenting cells, Nat Biotechnol, 18, 405, 10.1038/74455 · DOI · Paper page
- Schoenberger, 1998, Efficient direct priming of tumor-specific cytotoxic T lymphocyte in vivo by an engineered APC, Cancer Res, 58, 3094
- Levine, 1996, Antiviral effect and ex vivo CD4+ T cell proliferation in HIV-positive patients as a result of CD28 costimulation, Science, 272, 1939, 10.1126/science.272.5270.1939 · DOI · Paper page
- Tham, 2001, Activation of antigen-specific T cells by artificial cell constructs having immobilized multimeric peptide-class I complexes and recombinant B7-Fc proteins, J Immunol Methods, 249, 111, 10.1016/S0022-1759(00)00335-5 · DOI
- Shalaby, 2004, Absorbable microparticulate cation exchanger for immunotherapeutic delivery, J Biomed Mater Res B Appl Biomater, 69, 173, 10.1002/jbm.b.20040 · DOI
- van Rensen, 1999, Liposomes with incorporated MHC class II/peptide complexes as antigen presenting vesicles for specific T cell activation, Pharm Res, 16, 198, 10.1023/A:1018864005620 · doi:10.1023/a:1018864005620
- Prakken, 2000, Artificial antigen-presenting cells as a tool to exploit the immune “synapse”, Nat Med, 6, 1406, 10.1038/82231 · DOI
- Thery, 2002, Exosomes: composition, biogenesis and function, Nat Rev Immunol, 2, 569, 10.1038/nri855 · DOI · Paper page
- Pardoll, 2002, Spinning molecular immunology into successful immunotherapy, Nat Rev Immunol, 2, 227, 10.1038/nri774 · DOI · Paper page
- Fyfe, 1995, Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy, J Clin Oncol, 13, 688, 10.1200/JCO.1995.13.3.688 · DOI · Paper page
- Schluns, 2003, Cytokine control of memory T-cell development and survival, Nat Rev Immunol, 3, 269, 10.1038/nri1052 · DOI · Paper page
- Riddell, 2007, Engineering antitumor immunity by T-cell adoptive immunotherapy, Hematology Am Soc Hematol Educ Program, 250, 10.1182/asheducation-2007.1.250 · DOI
- Yamaguchi, 1993, In vivo biocompatibility studies of medisorb(R) 65/35 D, L-lactide/glycolide copolymer microspheres, J Control Release, 24, 81, 10.1016/0168-3659(93)90169-6 · DOI
- Fahmy, 2005, Surface modification of biodegradable polyesters with fatty acid conjugates for improved drug targeting, Biomaterials, 26, 5727, 10.1016/j.biomaterials.2005.02.025 · DOI · Paper page
- Mahoney, 2001, Transplantation of brain cells assembled around a programmable synthetic microenvironment, Nat Biotechnol, 19, 934, 10.1038/nbt1001-934 · DOI
- Jain, 2000, The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices, Biomaterials, 21, 2475, 10.1016/S0142-9612(00)00115-0 · DOI · Paper page
- Hogquist, 1994, T cell receptor antagonist peptides induce positive selection, Cell, 76, 17, 10.1016/0092-8674(94)90169-4 · DOI · Paper page
- MacGlashan, 1985, Test of a theory relating to the cross-linking of IgE antibody on the surface of human basophils, J Immunol, 135, 4129, 10.4049/jimmunol.135.6.4129 · doi:10.4049/jimmunol.135.6.4129
- Stone, 2001, T-cell activation by soluble MHC oligomers can be described by a two-parameter binding model, Biophys J, 81, 2547, 10.1016/S0006-3495(01)75899-7 · DOI
- Fahmy, 2001, Increased TCR avidity after T cell activation: a mechanism for sensing low-density antigen, Immunity, 14, 135
- Mescher, 1992, Surface contact requirements for activation of cytotoxic T lymphocytes, J Immunol, 149, 2402, 10.4049/jimmunol.149.7.2402 · DOI
- Deeths, 1997, B7-1-dependent co-stimulation results in qualitatively and quantitatively different responses by CD4+ and CD8+ T cells, Eur J Immunol, 27, 598, 10.1002/eji.1830270305 · DOI
- van de Weert, 2000, Protein instability in poly(lactic-co-glycolic acid) microparticles, Pharm Res, 17, 1159, 10.1023/A:1026498209874 · DOI · Paper page
- Cohen, 1991, Controlled delivery systems for proteins based on poly(lactic/glycolic acid) microspheres, Pharm Res, 8, 713, 10.1023/A:1015841715384 · DOI · Paper page
- Garlie, 1999, T cells coactivated with immobilized anti-CD3 and anti-CD28 as potential immunotherapy for cancer, J Immunother, 22, 336, 10.1097/00002371-199907000-00007 · doi:10.1097/00002371-199907000-00007
- Gattinoni, 2005, Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells, J Clin Invest, 115, 1616, 10.1172/JCI24480 · DOI · Paper page
- Oelke, 2005, Artificial antigen-presenting cells: artificial solutions for real diseases, Trends Mol Med, 11, 412, 10.1016/j.molmed.2005.07.005 · DOI
- Gopferich, 1996, Mechanisms of polymer degradation and erosion, Biomaterials, 17, 103, 10.1016/0142-9612(96)85755-3 · DOI · Paper page
- Boyman, 2006, Selective stimulation of T cell subsets with antibody-cytokine immune complexes, Science, 311, 1924, 10.1126/science.1122927 · DOI · Paper page
- Scheffold, 2007, Competition for cytokines: T(reg) cells take all, Nat Immunol, 8, 1285, 10.1038/ni1207-1285 · DOI
Cited by
Nanoparticle-Based Immunotherapy for Cancer
Shao, K., Singha, S., Clemente-Casares, X., Tsai, S., Yang, Y., & Santamaria, P. (2015) · ACS Nano · doi:10.1021/nn5062029 · Cited by 470
Biomaterials and emerging anticancer therapeutics: engineering the microenvironment
Gu, L., & Mooney, D. J. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2015.3 · Cited by 407
Nanoparticle Drug Delivery Systems Designed to Improve Cancer Vaccines and Immunotherapy
Fan, Y., & Moon, J. (2015) · Vaccines · doi:10.3390/vaccines3030662 · Cited by 275
The impact of nanoparticle ligand density on dendritic-cell targeted vaccines
Bandyopadhyay, A., Fine, R. L., Demento, S., Bockenstedt, L. K., & Fahmy, T. M. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2010.12.054 · Cited by 141
Self-citationForeign body response to synthetic polymer biomaterials and the role of adaptive immunity
Kyriakides, T. R., Kim, H.-J., Zheng, C., Harkins, L., Tao, W., & Deschenes, E. (2022) · Biomedical Materials · doi:10.1088/1748-605x/ac5574 · Cited by 106
Metadata
- Authors
- Steenblock, E. R., & Fahmy, T. M.
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 16
- Issue
- 4
- Pages
- 765-772
- ISSN
- 1525-0016 (ISSN-L)
- OpenAlex
- W1976027404
- Cited by
- 187
- References
- 2
- FWCI
- 2.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- creativecommons.org/licenses/by-nc-nd/4.0/ (vor, 3111 d)
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