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WT1 PEPTIDE VACCINATION IN COMBINATION WITH IMATINIB THERAPY FOR A PATIENT WITH CML IN THE CHRONIC PHASE

Please read the full article- this looks extremely promising
Sandy

Clinical efficacy of WT1 peptide vaccination
A 51 year-old male with CML in chronic phase had been treated with 400 mg imatinib for two and a half years. Although bcr-abl transcripts decreased transiently to less than 1,000 copies in 1 μg RNA extracted from PB cells (3-log reduction = 280 copies in 1 μg cellular RNA; median in our laboratory, n=120) during the imatinib treatment, the transcripts gradually increased to more than 4,000 copies spontaneously thereafter. Imatinib was increased to a dose of 600 mg and continued for 4 months, which caused adverse effects such as worsening of anemia and limb pain with increased CK. Therefore the dose of imatinib was decreased to 400 mg. Thereafter bcr-abl transcripts decreased transiently to 500 copies during the imatinib treatment, which was speculated to be the late effects of imatinib therapy at the dose of 600 mg a day. However, bcr-abl transcripts gradually increased to more than 1,000 copies thereafter. Since the patient was HLA-A*2402+ and informed consent was obtained, modified-type WT1 peptides, which had been identified to possess an anti-tumor immunogenicity [7], were administered subcutaneously at the dose of 1 mg every 2 weeks in combination with 400 mg imatinib. After the second administration of the peptides, WT1 peptide/HLA-A*2402 (WT1/MHC) tetramer+CD8+ T cells began to be detected in PB at a frequency of 7x10-6 in PB-CD8+ T cells. After the fourth administration of WT1 peptides, bcr-abl transcripts decreased to 820 copies with an increase in the frequency of WT1/MHC tetramer+CD8+ T cells in PB. However, bcr-abl transcripts increased to more than 1,000 copies after the eighth administration of WT1 peptides, though the frequencies of WT1/MHC tetramer+CD8+ T cells in PB were maintained at a considerable level. Since there was a report that some anti-tumor CD8+ CTLs lose their cytolytic activity by strong antigenic stimulation [9], the interval of WT1 peptide administration was changed from two weeks to four weeks after the eleventh administration of WT1 peptides. Although bcr-abl transcripts rose up to 2,600 copies after 12th administration of WT1 peptides, thereafter the transcripts tended to decrease and fell to 400 copies after 22nd administration of WT1 peptides. After seven months from the cessation of WT1 peptide vaccination bcr-abl transcripts decreased to the level of a major molecular response (170 copies). Four months thereafter, bcr-abl transcripts achieved to the level below detection by RQ/RT-PCR (complete molecular response) (Fig. 1). WT1/MHC tetramer+CD8+ CTLs are still present in the blood on 14th month post cessation of the peptides. No adverse effects due to WT1 peptide vaccination was observed except for skin induration and redness at the sites of WT1 peptide injection.

http://www.medsci.org/v07p0072.htm