P4.06 - Long-term molecular remission with an increase of WT1-specific CTLs after cessation of WT1 peptide vaccination in a patient with CML

Abstract

ABSTRACT Background: In order to clarify the safety and effectiveness of WT1 peptide vaccination for the patients with CML, we started WT1 peptide vaccination in combination with imatinib therapy for a patient with CML. Materials and Methods: A 51 years-old male with CML in CP had been treated with 400 mg imatinib for 2.5 years. Bcr-abl transcripts decreased transiently but gradually increased to more than 1, 000 copies thereafter. HLA-A*2402-restricted 9mer mutant WT1 peptides (CYTWNQMNL; a.a. 235-243), which had been identified to possess an anti-tumor immunogenicity, were administered subcutaneously at the dose of 1 mg/day every 2 weeks in combination with 400 mg imatinib for first 5 months and thereafter every 4 weeks for 12 months. The vaccination was undertaken 22 times totally. The appearance of WT1-specific CTLs in PB was confirmed by evaluating the frequency of MHC/WT1 tetramer + CD8+ T cells by using mixed lymphocyte peptide culture (MLPC). Results: Although bcr-abl transcripts increased up to more than 2,000 copies after the the initiation of WT1 vaccination every 2 weeks, the transcripts have decreased to less than 500 copies by the administration of WT1 peptides every 4 weeks. After seven months from the cessation of WT1 peptide vaccination bcr-abl transcripts decreased to the level of major molecular response (MMR), which is lasting thereafter for nearly 4 years. While WT1-specific CTLs were not detected in PB before WT1 peptide vaccination, the CTLs appeared after the second vaccination and remained at the level of nearly 15/106 CD8+ cells thereafter. The MHC/WT1 tetramer+ cells showed cytotoxicity against only leukemia cells expressing WT1 and HLA-A*2402. Conclusions: The present study showed that WT1 peptide vaccination for an imatinib-pretreated CML patient is feasible and effective, which is due to the long-lasting amplification of WT1-specific CTLs with cytotoxicity against WT1-expressing leukemia cells.