Impact Of Mature Dendritic Cells Pulsed With A Novel Wt1 Helper Peptide On The Induction Of Hla-A2-Restricted Wt1-Reactive Cd8(+) T Cells

The proliferation and activation of CD4(+) T helper 1 (Th1) cells and CD8(+) cytotoxic T lymphocytes (CTLs) that produce interferon-gamma (IFN-gamma) is an essential action of effective cancer vaccines. Recently, a novel Wilms' tumor 1 (WT1) helper peptide (WT1 HP34-51; amino acid sequence, WAPVLDFAPPGASAYGSL) applicable for various human leukocyte antigen (HLA) subtypes (HLA-DR, HLA-DP and HLA-DQ) was reported to increase peptide immunogenicity; however, the function of WT1 HP34-51 remains unclear. In the present study, mature dendritic cells (mDCs) pulsed with WT1 HP34-51 (mDC/WT1 HP34-51) activated not only WT1-specific CD4(+) T cells but also CD8(+) T cells that produced IFN-gamma following stimulation with immature dendritic cells (imDCs) pulsed with WT1 killer peptide (imDC/WT1 KP37-45) in an HLA-A*02:01- or HLA-A*02:06-restricted manner. Furthermore, the activated WT1-reactive CD4(+) Th1 cells were predominantly effector memory (EM) T cells. In 5 of 12 (41.7%) patients with cancer carrying the HLA-A*02:01 or HLA-A*02:06 allele, WT1-reactive CD8(+) T cells stimulated with mDC/WT1 HP34-51 enhanced their levels of WT1 KP37-45-specific IFN-gamma production, with an increase >10%. Simultaneous activation of CD4(+) and CD8(+) T cells occurred more often when stimulation with mDC/WT1 HP34-51 was combined with imDC/WT1 KP37-45 restimulation. These results indicated that the novel mDC/WT1 HP34-51 combination induced responses by WT1-specific EM CD4(+) Th1 cells and HLA-A*02:01- or HLA-A*02:06-restricted CD8(+) CTLs, suggesting its potential as a WT1-targeting cancer vaccine.