Supplementary Material for: Wilms' Tumor Gene 1 (WT1) Peptide Vaccine Therapy for Hematological Malignancies: From CTL Epitope Identification to Recent Progress in Clinical Studies Including a Cure-Oriented Strategy

The identification of human Wilms’ tumor gene 1 (WT1) protein-derived cytotoxic T lymphocyte (CTL) epitopes and the in vivo efficacy of WT1 peptide-based immunotherapy in a mouse model were reported in 2000. This successful basic research led to clinical studies of a WT1 peptide vaccine, and a positive impact on clinical response was first demonstrated in 2003 in the form of a reduction in blast cells of vaccine-treated patients with myelodysplastic syndromes (MDS). Since then, data on WT1 peptide vaccine-treated patients with immunological and/or clinical response have been accumulated. MDS and acute myeloid leukemia were the major target diseases to provide proof of concept for the therapeutic potential of the WT1 peptide vaccine. WT1 vaccination-induced clinical responses or usefulness were also shown for chronic myeloid leukemia, multiple myeloma, and acute lymphoblastic leukemia, as well as various types of solid cancers. Non-Hodgkin’s lymphoma and myeloproliferative neoplasms may also be target diseases because of their WT1 expression. Of note, recent clinical studies have demonstrated that patients with hematological malignancies who have minimal residual disease after chemotherapy or allogeneic hematopoietic stem cell transplantation may be cured by WT1 Peptide vaccination. Further enhancement of the efficacy and usefulness of the WT1 peptide vaccine is expected.

2000年，研究人员首次报道了人肾母细胞瘤基因1（Wilms’ tumor gene 1, WT1）蛋白衍生的细胞毒性T淋巴细胞（cytotoxic T lymphocyte, CTL）表位的鉴定结果，以及基于WT1肽的免疫疗法在小鼠模型中的体内疗效。这项具有里程碑意义的基础研究推动了WT1肽疫苗的临床研究，并于2003年首次证实其临床获益：接受疫苗治疗的骨髓增生异常综合征（myelodysplastic syndromes, MDS）患者体内原始细胞比例显著降低。自此，关于接受WT1肽疫苗治疗并获得免疫学应答和/或临床应答的患者的相关研究数据持续积累。骨髓增生异常综合征与急性髓系白血病是验证WT1肽疫苗治疗潜力的核心靶疾病，为其提供了概念验证依据。研究还证实，WT1疫苗接种对慢性髓系白血病、多发性骨髓瘤、急性淋巴细胞白血病及多种实体癌均可诱导临床应答，或具备临床应用价值。由于非霍奇金淋巴瘤与骨髓增殖性肿瘤均表达WT1，二者也有望成为WT1肽疫苗的靶疾病。值得注意的是，近期临床研究表明，化疗或异基因造血干细胞移植后仍存在微小残留病的血液系统恶性肿瘤患者，可通过WT1肽疫苗接种实现治愈。未来，WT1肽疫苗的疗效与临床应用价值有望得到进一步提升。