WT1 vaccine therapy against AML: Combination strategy for the next step

Identification: Nakata, Jun


Description

WT1 vaccine therapy against AML: Combination strategy for the next step
 
Jun Nakata1, Hiroko Nakajima2, Yoshiki Nakae3, Soyoko Morimoto1, Fumihiro Fujiki2, Sumiyuki Nishida4, Naoki Hosen5, Akihiro Tsuboi1, Yusuke Oji6, Yoshihiro Oka5, Atsushi Kumanogoh4, Haruo Sugiyama2
1Department of Cancer Immunotherapy, 2Cancer Immunology, 4Respiratory Medicine, Allergy and Rheumatic Disease, 5 Cancer Stem Cell Biology, 6Functional Diagnostic Science, Osaka University Graduate School of Medicine
3Department of Haematology, Nissay Hospital
 
We have reported the clinical outcome and immunological features of a phase 2 clinical study (UMIN-ID: 000015870) of WT1 peptide vaccine therapy, focusing on AML patients who attained hematological CR after chemotherapy but were at high risk of relapse1,2. The 2-year overall survival in our study was approximately 40% and the higher frequencies and clonal expansion of WT1-specific CTLs before WT1-specific CTLs were associated with the better clinical outcome.
 
Next we are exploring the way to enhance these anti-leukemia effects of WT1 peptide vaccine therapy by using mouse leukemia models. We identified the WT1 helper peptide array and confirmed that this WT1 helper peptide could induce higher Th1 response when combined with WT1 peptide vaccine therapy and also showed the higher anti-leukemia effect both in vitro and in vivo. We also tried the combination of CpG adjuvant, anti-CTLA4 antibody and anti-PD1 antibody together with the WT1 peptide and WT1 helper peptide vaccines. Only anti-PD1 antibody could enhance the WT1-specific CTL response and show the higher anti-leukemia effect in our mouse model. Our results suggested that combination of peptide vaccine with anti-PD1 antibody might be a good strategy in future.
 
References
  1. Wilms tumour 1 peptide vaccine as a cure-oriented post-chemotherapy strategy for patients with acute myeloid leukaemia at high risk of relapse. Nakata J et al. Br J Haematol 2017 May 23
  2. Wilms' Tumor Gene 1(WT1) peptide vaccine therapy for hematological malignancies: From CTL epitope identification to recent progress in clinical studies including a cure-oriented strategy. Oka Y et al. Oncol Res Treat 2017 Oct 18;40(11)
     
    Funding
    Grant-in-aid for young scientists (B) of Japan society for the promotion of science (JSPS)
     

Credits

Credits: None available.

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