¹Department of Biomedical Engineering, Yale University, New, Haven, Connecticut, USA

Correspondence: Tarek M. Fahmy, 55 Prospect Street, Room No. 412, New Haven, Connecticut 06511, USA. E-mail: tarek.fahmy@yale.edu

Received 26 July 2007; Accepted 7 January 2008; Published online 4 March 2008.

Abstract

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.