Antigen presentation on artificial acellular substrates: modular systems for flexible, adaptable immunotherapy

Abstract

Background: Recent findings on T cells and dendritic cells have elucidated principles that can be used for a bottom-up approach to engineering artificial antigen presentation on synthetic substrates. Objective/methods: To compare the latest artificial antigen-presenting cell (aAPC) technology, focussing on acellular systems because they offer advantages such as easy tunability and rapid point-of-care application compared with cellular systems. We review acellular aAPC performance and discuss their promise for clinical applications. Results/conclusion: Acellular aAPCs are a powerful alternative to naturalcell-based therapies, offering flexibility and modularity for incorporation oSf a variety of stimuli, hence increasing precision. Current technologies should adapt physiologically important signals within safe materials to more closely approximate their cellular counterparts. These constructs could be administered parenterally as APC replacements for active vaccines or used ex vivo for adoptive immunotherapy.

An Artificial Antigen-presenting Cell with Paracrine Delivery of IL-2 Impacts the Magnitude and Direction of the T Cell Response

“…The source of IL-2 is also relevant because activated CD4ϩ T cells may sometimes display FasL, which can result in CD8ϩ T cell death. Here we constructed a polymeric artificial antigen-presenting cell (paAPC) from biodegradable materials that is capable of providing an antigenic signal, effective costimulation, and adjustable paracrine IL-2 signals to T cells (17,18). The polymer that constitutes the core of this system, poly(lactic co-glycolic acid), and its homopolymers poly(lactic acid) and poly(glycolic acid) have been used for over 30 years in various human clinical applications, including drug delivery systems.…”

Enhancement of the antigen-specific cytotoxic T lymphocyte-inducing ability in the PMDC11 leukemic plasmacytoid dendritic cell line via lentiviral vector-mediated transduction of the caTLR4 gene

“…Although autologous monocyte-derived DCs (moDCs) are commonly used as APCs for use in immunotherapy, the preparation of a sufficiently large quantity is complex and the quality of moDCs varies between individuals (12). Artificial APCs using either acellular (13–16) or cell-based systems [e.g., Drosophila (17), mouse fibroblast (18,19), human erythro-myeloid (20,21) or breast carcinoma (22) cell lines] have been introduced in place of moDCs. In these cell-based artificial APCs, antigen presentation-associated molecules, including major histocompatibility class I (17–21), CD80 (17–19,21,22), intercellular adhesion molecule 1 (CD54) (17–19,21), lymphocyte function-associated antigen 3 (CD58) (18,19,21) or CD83 (21) require expression via cDNA transfection in order to reach sufficient levels of antigen-presenting ability on these artificial APCs.…”

Improving Adoptive T Cell Therapy: The Particular Role of T Cell Costimulation, Cytokines, and Post-Transfer Vaccination

“…This suggests that cytokine cocktails can be used to reprogram late differentiated T cells. Besides delivery of cytokine-mediated signals via cytokine supplementation to the cultures, aAPCs can be designed to express cytokines or T cells can be triggered or engineered to produce abundant cytokines themselves (99, 112–114). The advantage of aAPCs is that they can be designed to simultaneously provide costimulation and cytokine-mediated signals (112, 115).…”