Abstract 3659: WT1 and PRAME mRNA transfected TLR 7/8-polarized fast DC vaccines in AML patients mount specific immune responses and impact progression free survival
Authors: Iris Bigalke, Guri Solum, Dag Josefsen, Yngvar Fløisand, Kirsti Hønnåshagen, Lisbeth Skoge, Signe Spetalen, Stein Sæbøe-Larssen, Dolores J. Schendel, Gunnar Kvalheim
Journal: Cancer Research (2017)

Abstract Patients diagnosed with acute myeloid leukemia (AML) may not be eligible for curative intensive treatment due to co-morbidity factors or age. Here we report results of 5 AML patients in morphological remission after incomplete induction/consolidation chemotherapy treated with dendritic cells (DCs) targeting WT-1 and PRAME. DCs were produced as described previously (Subklewe et al 2014), using a maturation cocktail containing the TLR 7/8 ligand R848. These DCs show a polarized release of IL-12p70 combined with low IL-10 upon stimulation. 2.5 or 5E+6 DCs per antigen were injected intradermally once weekly for 4 weeks (wks), in wk 6 and thereafter at monthly intervals. Blood and bone marrow (BM) samples were collected at regular intervals. Minimal residual disease (MRD) was measured in BM by quantitative PCR of WT-1 and PRAME expression and by morphology. Immune responses were assessed by analysis of intracellular interferon gamma expression or proliferation following stimulation with peptides spanning WT-1, PRAME, hTERT and survivin or after stimulation with autologous WT-1 and PRAME DCs. A 57 year old woman with intermediate risk M4 AML was vaccinated over 22 months after chemotherapy. Five weeks after start of vaccination she mounted strong CD8 responses against PRAME combined with an increase in hTERT response, suggesting epitope spreading. WT-1 signals in BM showed low positive levels throughout vaccination, but she remains in morphological remission 33 months after end of chemotherapy (EoC). A 50 year old man with M2 intermediate risk AML, initially not eligible for BM transplantation, showed specific immune responses against WT-1 during 10 months of vaccination. Due to Bell’s Palsy he was treated with cortisone which immediately reduced the vaccine effect, accompanied by increase of blasts in the bone marrow. Following new induction therapy he received BM transplantation and is currently in CR. A 68 year old woman with M1 intermediate risk AML is under vaccination for 24 months. WT-1 signals in BM continue to be slightly elevated without any sign of morphological relapse. CD4 responses and low CD8 responses are detected against WT-1, PRAME and hTERT. A 73 year old woman with M1 good risk AML relapsed after 6 months of DC vaccination without mounting specific immune responses. DC treatment was combined with 5-Azacytidine without any immunological and clinical effects. A 59 year old woman with good risk AML has been vaccinated for 14 months and is in remission for 21 months since EoC. WT-1 in BM remains slightly elevated whilst the initially positive PRAME signal is negative. Our results show that in 4 out of 5 AML patients fast TLR-polarized DC vaccination induced or supported specific T cell responses. 3 patients continue to be in CR after 21, 25 and 33 months respectively, following suboptimal primary chemotherapy. Immune responses are under investigation and will be presented. Citation Format: Iris Bigalke, Guri Solum, Dag Josefsen, Yngvar Fløisand, Kirsti Hønnåshagen, Lisbeth Skoge, Signe Spetalen, Stein Sæbøe-Larssen, Dolores J. Schendel, Gunnar Kvalheim. WT1 and PRAME mRNA transfected TLR 7/8-polarized fast DC vaccines in AML patients mount specific immune responses and impact progression free survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3659. doi:10.1158/1538-7445.AM2017-3659