Abstract
The Wilms tumor gene WT1 is highly expressed not only in hematopoietic malignancies, including leukemia and myelodysplastic syndromes (MDS), but also in various kinds of solid tumors, including lung, breast, and colorectal cancer. Human cytotoxic T lymphocytes (CTLs) which could specifically lyse WT1-expressing tumor cells with HLAA* 0201 or HLA-A*2402 restriction were generated in vitro. We have also demonstrated that mice immunized with the WT1 peptide rejected challenges by WT1-expressing tumor cells and survived with no signs of auto-aggression to normal organs which physiologically expressed WT1 both in prophylactic and therapeutic models. Furthermore, we and others recently detected IgM and IgG WT1 antibodies in the patients with hematopoietic malignancies, indicating that WT1 protein was highly immunogenic, and that WT1-specific cellular immune responses that induce immunoglobulin classswitch of WT1 antibodies were elicited in the patients. These results provided us with the rationale for elicitation of CTL responses targeting the WT1 product for cancer immunotherapy. On the basis of the findings mentioned above, we performed a phase I clinical trial of WT1 peptide cancer vaccine for the patients with malignant neoplasms. It was demonstrated that WT1 peptide cancer vaccine had efficacy in the clinical setting, because reduction of leukemic blast cells, decrease of tumor markers, or regression of tumor masses was observed after the WT1 vaccination in patients with hematopoietic malignancies or solid cancers.
Keywords: cytotoxic T lymphocytes cells, hematopoietic malignancies, HLA class I, immunotherapy, granulocyte-colony stimulating factor (G-CSF), WT1 vaccination
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