WT1 peptide vaccination in combination with imatinib therapy for a patient with CML in the chronic phase.
Although tyrosine kinase inhibitors is effective for dramatically reducing CML cells, it might be difficult to eradicate completely the CML stem cells. We aimed to clarify the safety and effects of WT1 peptide vaccination in combination with imatinib therapy for a CML patient. A 51 year-old male with CML in CP, who showed a resistance against imatinib therapy for 2.5 years, began to be treated with 9 mer modified-type WT1 peptides in combination with standard dose of imatinib. Although every 2-week-administration of WT1 peptides for 22 weeks did not show definite effects on the quantification of bcr-abl transcripts, by changing the administration from every 2 weeks to 4 weeks bcr-abl transcripts decreased remarkably. After 11 months of every 4-week-administration of the peptides and 12 months post cessation of the peptides bcr-abl transcripts achieved to the level below detection by RQ/RT-PCR (complete molecular response). WT1/MHC tetramer(+)CD8(+) CTLs, which appeared after the second administration of WT1 peptides and remained more than 15 in number among 10(6) CD8(+) T cells throughout the administration of WT1 peptides, are still present in the blood on 14th month post cessation of the peptides. An in vitro study as to the cytotoxicity of lymphocytes induced by mixed lymphocyte peptide culture demonstrated that cultured lymphocytes possessed cytotoxicity against WT1 expressing leukemia cells and the cytotoxicity was WT1-specific and MHC class I restricted. The present study showed that WT1 peptide vaccination in combination with TKI is feasible and effective in the therapy for imatinib-resistant CML.
Narita
Miwako
M
Laboratory of Hematology and Oncology, Graduate School of Health Sciences, Niigata University, Niigata, Japan. naritami@clg.niigata-u.ac.jp
Masuko
Masayoshi
M
Kurasaki
Tohri
T
Kitajima
Toshiki
T
Takenouchi
Shoko
S
Saitoh
Anri
A
Watanabe
Norihiro
N
Furukawa
Tatsuo
T
Toba
Ken
K
Fuse
Ichiro
I
Aizawa
Yoshifusa
Y
Kawakami
Manabu
M
Oka
Yoshihiro
Y
Sugiyama
Haruo
H
Takahashi
Masuhiro
M
D001549:Benzamides; D016044:Fusion Proteins, bcr-abl / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000235:genetics; D010879:Piperazines; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011743:Pyrimidines; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000378:metabolism; D014611:Vaccination; D025721:WT1 Proteins / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics
D001549:Benzamides; D010455:Peptides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D025721:WT1 Proteins; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl