A clinical and immunologic phase 2 trial of Wilms tumor gene product 1 (WT1) peptide vaccination in patients with AML and MDS

CML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors

“…[20][21][22] A phase 1 trial (NCT02011945) of dasatinib and nivolumab, a PD-1 inhibitor, is recruiting, with MMR and DMR incidence as planned outcome measures. LAAs such as WT1, PRAME, PR3, and BMI-1 in CML patients represent attractive targets for immunotherapy, [23][24][25][26][27][28][29] with efficacy demonstrated in vaccination, including dendritic cell vaccination, [30][31][32][33] and, more recently, T-cell receptor-mimic antibodies. [34][35][36] In support of these studies, we observed maximal restoration of immune recovery, as demonstrated by increased effector NK cell and T-cell immune responses, reduced PD-1 inhibitory molecule expression on CD4 1 and CD8 1 T cells, and reduced numbers of Mo-MDSC in MR 4.5 only, suggesting DMR may be the preferred threshold for future TFR studies to benefit from the improved effector immune responses.…”

Prophylactic transfer of BCR-ABL–, PR1-, and WT1-reactive donor T cells after T cell–depleted allogeneic hematopoietic cell transplantation in patients with chronic myeloid leukemia

“…In normal peripheral blood, WT1 is not detectable in our hands (⌬C t Ͼ 25 cycles), in the 4 patients (nos. [11][12][13][14] analyzed, the ⌬C t values were 8.9, 15.6, 17.9, and 22.6. However, only the first patient could be analyzed at diagnosis; the others were investigated during follow-up.…”

“…9,10 Peptide-based vaccination trials with regard to both PR1 and WT1 have demonstrated clinical responses, and an association between therapeutic response and increased frequency of WT1-specific CTL was reported. 8,11,12 In contrast to the aforementioned leukemia-associated antigens, the B-cell receptor-ABL fusion protein represents a tumor-specific antigen expressed in CML stem and progenitor cells but not in healthy hematopoietic stem cells (HSCs). Several studies have demonstrated that CD8 ϩ T cells reactive against B-cell receptor-ABL-derived peptides can be generated in vitro and are able to lyse peptide-loaded target cells or CML cells.…”

WT1 peptide vaccination following allogeneic stem cell transplantation in pediatric leukemic patients with high risk for relapse: successful maintenance of durable remission

“…[1][2][3][4] However, there is no published data evaluating the role of BAALC in the hematopoietic system. BAALC is located on human chromosome 8q22.3 and is highly conserved in mammals.…”