Portal de Periódicos da CAPES

A WT1 protein‐derived, naturally processed 16‐mer peptide, WT1 332 , is a promiscuous helper peptide for induction of WT1‐specific Th1‐type CD4 + T cells

2008; Wiley; Volume: 52; Issue: 12 Linguagem: Inglês

10.1111/j.1348-0421.2008.00080.x

1348-0421

Fumihiro Fujiki, Yoshihiro Oka, Mai Kawakatsu, Akihiro Tsuboi, Hiroko Nakajima, Olga A. Elisseeva, Yukie Harada, Zheyu Li, N Tatsumi, Eriko Kamino, Toshiaki Shirakata, Sumiyuki Nishida, Yuki Taniguchi, Ichiro Kawase, Yusuke Oji, Haruo Sugiyama,

CAR-T cell therapy research

ABSTRACT The Wilms' tumor gene WT1 is overexpressed in various tumors, and the WT1 protein has been demonstrated to be an attractive target antigen for cancer immunotherapy. A WT1 protein‐derived 16‐mer peptide, WT1 332 (KRYFKLSHLQMHSRKH), which was naturally generated through processing in cells and could elicit Th1‐type CD4 + helper T cell responses with an HLA‐DRB1*0405‐restriction has previously been identified by us. In the present study, it has been demonstrated that WT1 332 can induce WT1 332 ‐specific CD4 + T cell responses with the restriction of not only HLA‐DRB1*0405 but also HLA‐DRB1*1501, ‐DRB1*1502, or ‐DPB1*0901. These HLA class II‐restricted WT1 332 ‐specific CD4 + T cell lines produced IFN‐γ but neither IL‐4 nor IL‐10 with WT1 332 stimulation, thus showing a Th1‐type cytokine profile. Furthermore, HLA‐DRB1*1501 or ‐DRB1*1502‐restricted WT1 332 ‐specific CD4 + T cell lines responded to WT1‐expressing transformed cells in an HLA‐DRB1‐restricted manner, which is consistent with our previous finding that WT1 332 is a naturally processed peptide. These results indicate that the natural peptide, WT1 332 , is a promiscuous WT1‐specific helper epitope. WT1 332 is expected to apply to cancer patients with various types of HLA class II as a WT1‐specific helper peptide in combination with HLA class I‐restricted WT1 peptides.