Artificial antigen-presenting cells have been shown to stimulate antigen-specific T-cell responses, but their effect in vivo may be compromised by rapid macrophage clearance. In a study reported in Clinical Cancer Research, Bruns and colleagues added CD47 to classic two-signal artificial antigen-presenting cells to produce a three-signal “don’t eat me” artificial antigen-presenting cell that might better avoid macrophage uptake and clearance.
Control artificial antigen-presenting cells and the CD47-positive antigen-presenting cells were analyzed in vitro in human primary T-cell and macrophage co-cultures and compared in vivo in a NOD/SCID T-cell proliferation model and a B16-SIY melanoma model. In culture with human macrophages, CD47-positive antigen-presenting cells exhibited CD47 concentration-dependent inhibition of phagocytosis with no reduction in their ability to generate and expand antigen-specific T cells; the T cells generated by these antigen-presenting cells had killing abilities and polyfunctionality equivalent to those of control antigen-presenting cell–generated T cells. In in vivo studies, CD47-positive antigen-presenting cells exhibited increased stimulatory capacity and tumor inhibition compared with control antigen-presenting cells.
The investigators concluded: “Our data for the first time show that [artificial] antigen-presenting cells functionalized with CD47 maintain their stimulatory capacity in vitro and demonstrate enhanced in vivo efficiency. Thus, this next generation [artificial] APCCD47+ has a unique potential to enhance the application of the [artificial] antigen-presenting cell technology for future immunotherapy approaches.” ■
Bruns H, et al: Clin Cancer Res. January 15, 2015 (early release online).