Abstract
Background: It has been demonstrated that the Wilms Tumor gene (WT1) is highly expressed in various types of leukaemia. WT1 expression level reflects the extent of minimal residual disease and significantly increases at relapse. Proteinase 3 (Pr3) is an aberrantly expressed myeloid leukaemia protein and T cells with specificity for both, Wt1 and Pr3 derived antigens, have been generated in vitro from healthy individuals and cancer patients and lysed myeloid leukaemic blasts. MUC1(CD227) is presented on a considerable amount of multiple myeloma cell lines and plasmocytoma cells. MUC1-derived HLA-class I/II epitopes represent universal tumor antigens, which are also expressed by malignant plasmocytoma cells and could be attacked by MUC1-specific CTLs.
Aims: We investigate safety and feasibility of a vaccination with WT1 and Pr3 or MUC1 derived peptides in patients suffering from AML or multiple myeloma, respectively. Thereby we asses the induction of tumor-antigen specific T-cells as well as clinical responses.
Methods: HLA A2.1 positive patients with AML/MDS <30% blasts in the bone marrow biopsy receive 6 injections of WT1 and Pr3derived peptides, combined with Montanide ISA51 (incomplete Freund’s adjuvants), PADRE and VaxImmune (CpG 7909). Vaccination is given every two weeks. HLA A2.1 positive patients with multiple myeloma Stage I, stable disease or partial remission after chemotherapy receive 6 injections of two different MUC1 derived peptides, VaxImmune and Montanide with or without PADRE. A total of ten patients will be treated in each trial. Safety and feasibility as well as clinical course is reassessed every visit. Induction of immune response is assessed by ELISPOT, Cr-release-Assays and FACS-analysis (Tetramer-staining).
Results: So far, 4 patients completed our ongoing AML-vaccination protocol; 5 patients were vaccinated in the myeloma-study. Local inflammatory responses at the injection site, such as redness, swelling and pain were observed in all patients (Grade 2). In one case, skin necrosis (Grade 2) and superinfection occurs. 4 out of 9 patients developed a systemic reaction including influenza-like symptoms and fever (Grade 1-2). 1 patient suffered from an anaphylactic reaction (Grade 3) after vaccination. Clinical response data have so far been analysed for patients vaccinated with Pr3 and WT1 derived peptides: Peripheral platelet counts of a patient suffering from MDS RAEB-T improved while blasts detected in the bone marrow remained stable, the FLT3-mutation (D835) was absent after 6 vaccinations (initial positive). 3 patients with refractory AML remained progressive even after six vaccinations. 4 out of 5 myeloma patients with MUC1 derived vaccine remained stable, 1 patient went progressive. Immunological analyses are pending and will be presented at the meeting.
Conclusion: Vaccination with WT1/ Pr3 or MUC1, PADRE, VaxImmune (CpG7909) and Montanide is safe and feasible, even in advanced disease and after multiple previous therapies, including stem cell transplantation. Observed local as well as systemic side effects were predominantly mild to moderate.
Disclosure: No relevant conflicts of interest to declare.
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