A comprehensive platform for ex vivo T-cell expansion based on biodegradable polymeric artificial antigen-presenting cells.
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.
Steenblock
Erin R
ER
Department of Biomedical Engineering, Yale University, New, Haven, Connecticut, USA.
Fahmy
Tarek M
TM
D000818:Animals; D017951:Antigen Presentation; D001711:Biotransformation; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation; D006801:Humans; D016219:Immunotherapy, Adoptive; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry* / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008863:Microspheres; D053758:Nanoparticles; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D007376:Interleukin-2; D011994:Recombinant Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid