Scaffolds that mimic antigen-presenting cells enable ex vivo expansion of primary T cells.

Abstract:

:Therapeutic ex vivo T-cell expansion is limited by low rates and T-cell products of limited functionality. Here we describe a system that mimics natural antigen-presenting cells (APCs) and consists of a fluid lipid bilayer supported by mesoporous silica micro-rods. The lipid bilayer presents membrane-bound cues for T-cell receptor stimulation and costimulation, while the micro-rods enable sustained release of soluble paracrine cues. Using anti-CD3, anti-CD28, and interleukin-2, we show that the APC-mimetic scaffolds (APC-ms) promote two- to tenfold greater polyclonal expansion of primary mouse and human T cells compared with commercial expansion beads (Dynabeads). The efficiency of expansion depends on the density of stimulatory cues and the amount of material in the starting culture. Following a single stimulation, APC-ms enables antigen-specific expansion of rare cytotoxic T-cell subpopulations at a greater magnitude than autologous monocyte-derived dendritic cells after 2 weeks. APC-ms support over fivefold greater expansion of restimulated CD19 CAR-T cells than Dynabeads, with similar efficacy in a xenograft lymphoma model.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Cheung AS,Zhang DKY,Koshy ST,Mooney DJ

doi

10.1038/nbt.4047

subject

Has Abstract

pub_date

2018-02-01 00:00:00

pages

160-169

issue

2

eissn

1087-0156

issn

1546-1696

pii

nbt.4047

journal_volume

36

pub_type

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