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Adenovirus vector delivery stimulates natural killer cell recognition

Peter Tomasec^1,

Eddie C. Y. Wang^2,

¹ Department of Medical Microbiology, Cardiff University, Heath Park, Cardiff CF14 4XY, UK
² Department of Medical Biochemistry and Immunology, Cardiff University, Heath Park, Cardiff CF14 4XY, UK
³ Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Avenue North, Seattle, WA98109, USA

Correspondence
Gavin W. G. Wilkinson
WilkinsonGW1{at}cardiff.ac.uk

We report that delivery of first-generation replication-deficient adenovirus (RDAd) vectors into primary human fibroblasts is associated with the induction of natural killer (NK) cell-mediated cytolysis in vitro. RDAd vector delivery induced cytolysis by a range of NK cell populations including the NK cell clone NKL, primary polyclonal NK lines and a proportion of NK clones (36 %) in autologous HLA-matched assays. Adenovirus-induced cytolysis was inhibited by antibody blocking of the NK-activating receptor NKG2D, implicating this receptor in this function. NKG2D is ubiquitously expressed on NK cells and CD8⁺ T cells. Significantly, -irradiation of the vector eliminated the effect, suggesting that breakthrough expression from the vector induces at least some of the pro-inflammatory responses of unknown aetiology following the application of RDAd vectors during in vivo gene delivery.

These authors contributed equally to this work.

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