Therapeutic Vaccine Combination May Help Patients with Myelodysplastic Syndrome
A new study demonstrates that it is possible to vaccinate patients with MDS against a decitabine-induced antigen and that the level of induced expression is sufficient to trigger cytotoxicity in patient-derived vaccine induced T-cells.
Abstract The hypomethylating agent decitabine induces expression of the cancer testis antigen NY-ESO-1 in the myeloid cells of patients with myelodysplastic syndrome (MDS). MDS patients treated with decitabine and an NY-ESO-1 vaccine developed NY-ESO-1-specific T cell responses directed against their abnormal myeloid cells, raising hopes for combinatorial immunotherapy of this disease. PMID: 29284705 [PubMed - as supplied by publisher]
Wilms’ tumor 1 (WT1) is constantly expressed in leukemic cells of acute leukemia and myelodysplastic syndrome (MDS). A T-cell receptor (TCR) that specifically reacts with WT1 peptide in the context of HLA-A*24:02 has been identified. We conducted a first-in-human trial of TCR–gene transduced T-cell (TCR–T-cell) transfer in patients with refractory acute myeloblastic leukemia (AML) and high-risk MDS to investigate the safety and cell kinetics of the T cells. The WT1-specific TCR-gene was transduced to T cells using a retroviral vector encoding small interfering RNAs for endogenous TCR genes. The T cells we...
WT4869 is a synthetic peptide vaccine derived from the Wilms’ tumor gene 1 (WT1) protein. This phase 1/2 open‐label study evaluated the safety and efficacy of WT4869, and biomarkers for response, in patients with myelodysplastic syndrome. WT4869 (5–1200 μg/dose) was administered intradermally every 2 weeks, according to a 3 + 3 dose‐escalation method in higher‐risk (International Prognostic Scoring System score ≥1.5) or lower‐risk (score
CONCLUSION: These data indicate that vaccination against induced NY-ESO-1 expression can produce an antigen-specific immune response in a relatively non-immunogenic myeloid cancer and highlight the potential for induced-antigen directed immunotherapy in a group of patients with limited options. PMID: 28947565 [PubMed - as supplied by publisher]
Abstract WT4869 is a synthetic peptide vaccine derived from the Wilms’ tumor gene 1 (WT1) protein. This phase 1/2 open‐label study evaluated the safety and efficacy of WT4869, and biomarkers for response, in patients with myelodysplastic syndrome. WT4869 (5–1200 μg/dose) was administered intradermally every 2 weeks, according to a 3+3 dose‐escalation method in higher‐risk (International Prognostic Scoring System score ≥1.5) or lower‐risk (score
Authors: Moulis G, Lapeyre-Mestre M, Adoue D, Sailler L Abstract During the last decade, the development of large clinical and population-based cohorts led to new findings in the epidemiology and the pharmacoepidemiology of immune thrombocytopenia (ITP). The incidence is estimated to 3-4 for 10(5) inhabitants/year, with a slight female predominance and peaks in children and patients after 60 years. The incidence rate is 9 for 10(5) inhabitants/year in males after 75 years. Variations across ethnic groups are discussed. In France, there is a North-South gradient and a peak of incidence during win...
PR1 peptide vaccine may benefit many patients with myeloid leukemia, chronic myeloid leukemia and myelodysplastic syndrome, findings from an early clinical trial suggest.Reuters Health Information
Even though the pathogenesis of myelodysplastic syndromes (MDS) is dominated by specific molecular defects involving hematopoietic precursors, also immune mechanisms seem to play a fundamental functional role. In this review we will first describe the clinical and laboratory autoimmune manifestations often detectable in MDS patients. We will then focus on studies addressing the possible influence of different immune cell subpopulations on the disease onset and evolution. We will finally consider therapeutic approaches based on immunomodulation, ranging from immunosuppressants to vaccination and transplantation strategies.
Authors: Frøsig TM Abstract This review is focused on research within three different areas of tumor immunology: discovery of new T-cell epitopes and a new immunological antigen (reported in Paper I and II), elucidation of the immunological effects of treatment with a hypomethylating drug (reported in Paper III) and discovery of new conditional ligands (reported in Paper IV). Many melanoma-associated T-cell epitopes have been described, but 45% of these are restricted to human leukocyte antigen (HLA)-A2, leaving the remaining 36 different HLA molecules with only a few described T-cell epitopes each. Therefor...
Abstract Wilms' tumor gene 1 (WT1) is overexpressed in leukemia and WT1‐ derived CD8+ T cell epitopes for immunotherapies targeting WT1 have been defined. Here, we analyzed expression of WT1 in 226 peripheral blood and bone marrow samples from patients with acute myeloid leukemia or myelodysplastic syndrome (AML/MDS) before and after allogeneic stem cell transplantation (SCT). Transcripts were assessed by quantitative Polymerase chain reaction, WT1‐specific CD8+ cytotoxic T cells (CTL) were monitored by tetramer staining and enzyme‐linked immunospot (ELISPOT) assays. Reduction of WT1 levels correlated with a longer survival (p