Human CLEC9A antibodies deliver Wilms' tumor 1 (WT1) antigen to CD141⁺ dendritic cells to activate naive and memory WT1-specific CD8⁺ T cells.

ABSTRACT:

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 line

SUBMITTER: Pearson FE 

PROVIDER: S-EPMC7292901 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature