WT1-specific serum antibodies in patients with leukemia

WT1 is an oncogenic protein expressed by the Wilms' tumor gene and overexpr essed in the majority of acute myelogenous leukemias (AMLs) and chronic mye logenous leukemias (CMLs), The current study analyzed the sera of patients with AML and CML for the presence of antibodies to full-length and truncate d WT1 proteins. Sixteen of 63 patients (25%) with AML had serum antibodies reactive with WT1/full-length protein. Serum antibodies from all 16 were al so reactive with WT1/NH2-terminal protein. By marked contrast, only 2 had r eactivity to WT1/COOH-terminal protein, Thus, the level of immunological to lerance to the COOH terminus may be higher than to the NH, terminus. The WT 1/COOH-terminal protein contains four zinc finger domains with homology to other self-proteins. By implication, these homologies may be related to the increased immunological tolerance. Results in patients with CML, were simi lar with antibodies reactive to WT1/full-length protein detectable in serum of 15 of 81 patients (19%), Antibodies reactive with WT1/NH2-terminal prot ein were present in the serum of all 15, whereas antibodies reactive with W T1/COOH-terminal protein were present in only 3. By contrast to results in leukemia patients, antibodies reactive with WT1/full-length protein were de tected in only 2 of 96 normal individuals, The greater incidence of antibod y in leukemia patients provides strong evidence that immunization to the WT 1 protein occurred as a result of patients bearing malignancy that expresse s WT1, These data provide further stimulus to test therapeutic vaccines dir ected against WT1 with increased expectation that the vaccines will be able to elicit and/or boost an immune response to WT1.