Impact of mature dendritic cells pulsed with a novel WT1 helper peptide on the induction of HLA‑A2‑restricted WT1‑reactive CD8+ T cells.

Abstract

The proliferation and activation of CD4+ T helper 1 (Th1) cells and CD8+ cytotoxic T lymphocytes (CTLs) that produce interferon‑γ (IFN‑γ) 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‑γ 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‑γ 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.