Clinical effects of Wilms tumor protein (WT) 1 peptide vaccination in patients with WT1-expressing solid tumors as compared to patients with AML/MDS.

Abstract

2560 Background: WT1 holds great promise for cancer immunotherapy, is expressed in many hematologic and solid malignancies, and is essential for tumor proliferation. After demonstrating good immunological and clinical efficacy of WT1 peptide vaccination in patients with active AML and MDS, we have initiated a vaccination trial for patients with WT1 expressing carcinomas. We here compare immunogenicity and clinical efficacy among carcinoma patients (CP) and AML/MDS patients. Methods: Patients with ovarian (n=8), thyroid (n=2), breast (n=1), gastric (n=1), and larynx cancer (n=1), astrocytoma (n=1) and mesothelioma (n=3) received 0.2mg HLA-A0201-restricted WT1.126-134 peptide admixed with 1 mg KLH (day 3), and 62.5µg GM-CSF (day 1-4). Quantitation of WT1 specific T cells was performed in peripheral blood (PB) of CP by tetramer staining and compared with analogue analyses in 25 AML/MDS patients. Results: Seventeen CP received a median of 11 vaccinations (range 1-35) and 12 of 17 are evaluable for T cell response. None of the 12 had WT1-specific T cells at baseline, in contrast to 28% of AML/MDS patients. After 4 vaccinations WT1-specific T cells were detectable in 67% of CP and in 54% of AML/MDS patients. After 6 vaccinations WT1-specific T cells were present in 40% of CP and in 78% of AML/MDS patients. Thus, the overall conversion rate was 75% in CP and 56% in AML/MDS. WT1 specific CD8+ T cells in most AML/MDS patients remained detectable during the course of vaccination, whereas in CP WT1 specific CD8+ T cells were only transient, despite of continuation of vaccination and ongoing clinical efficacy, which was demonstrated with 1 partial remission and 6 disease stabilisations between 2 and 22+ months. Conclusions: These results demonstrate profound differences in spontaneous and vaccine induced T cell response among patients with haematological and solid malignancies, suggesting considerably higher spontaneous immunogenicity of AML/MDS, but a higher conversion rate in CP. In contrast to AML/MDS WT1 specific T cells in PB of CP were despite ongoing clinical efficacy only transient, possibly due to migration into the tumor.