作者
Frances E Pearson, Kirsteen M Tullett, Ingrid M Leal‐Rojas, Oscar L Haigh, Kelly‐Anne Masterman, Carina Walpole, John S Bridgeman, James E McLaren, Kristin Ladell, Kelly Miners, Sian Llewellyn‐Lacey, David A Price, Antje Tunger, Marc Schmitz, John J Miles, Mireille H Lahoud, Kristen J Radford
发表日期
2020
期刊
Clinical & translational immunology
卷号
9
期号
6
页码范围
e1141
简介
Objectives
Vaccines that prime Wilms' tumor 1 (WT1)‐specific CD8+ T cells are attractive cancer immunotherapies. However, immunogenicity and clinical response rates may be enhanced by delivering WT1 to CD141+ dendritic cells (DCs). The C‐type lectin‐like receptor CLEC9A is expressed exclusively by CD141+ DCs and regulates CD8+ T‐cell responses. We developed a new vaccine comprising a human anti‐CLEC9A antibody fused to WT1 and investigated its capacity to target human CD141+ DCs and activate naïve and memory WT1‐specific CD8+ T cells.
Methods
WT1 was genetically fused to antibodies specific for human CLEC9A, DEC‐205 or β‐galactosidase (untargeted control). Activation of WT1‐specific CD8+ T‐cell lines following cross‐presentation by CD141+ DCs was quantified by IFNγ ELISPOT. Humanised mice reconstituted with human immune cell subsets, including a repertoire of naïve …
引用总数
2020202120222023202418967