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 Sugiyama^2
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 relapse^1,2. 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.
 
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