Enhancing the Wilms’ Tumor 1 (WT1) antigen expression and presentation by mRNA electroporated dendritic cells

Project Details

Description

The Wilms' Tumor protein 1 (WT1) has been characterized as a nearly universal tumor-associated antigen, being overexpressed in a variety of solid and hematological malignancies. This together with the limited expression of WT1 in normal tissues and its strong immunogenic potential, has rendered WT1 an attractive target for cancer immunotherapy. Dendritic cells, engineered to express WT1 by mRNA electroporation, have entered the clinical trial stage and represent promising candidates for immunotherapy. We have optimized a WT1-mRNA encoding plasmid using a step-by-step approach: flanking the WT1-sequence by the HLA class II-sorting signal of DC-LAMP to enhance presentation in both HLA class I and class II molecules; deletion of the nuclear localization sequence of WT1 to promote cytoplasmic expression; in silico optimization of the WT1-DNA sequence for maximizing translational efficiency; and finally cloning into an optimized vector. We succeeded in obtaining enhanced and prolonged cytoplasmic expression of WT1 in mRNA-electroporated DCs, which also resulted in improved presentation of WT1 epitopes to specific T-cells. To provide ultimate proof of the superiority of our novel mRNA-encoding construct, we would like to perform in vitro stimulations of WT1-specific T cells from a naïve or resting pool of T cells, and we would like to test its functionality in vivo in a murine model.
AcronymFWOKN238
StatusFinished
Effective start/end date1/01/1230/12/12

Keywords

  • Tonic Pain
  • Dendritic Cells
  • Evoked Potentials
  • Bispecific Antibodies
  • Immunotherapy
  • Immunology
  • Oncology

Flemish discipline codes

  • Basic sciences
  • Biological sciences
  • Materials engineering