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.
Source: CancerNetwork - Category: Cancer & Oncology Authors: Tags: Hematologic Malignancies Myelodysplastic Syndromes News Source Type: news

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Markus Hartl* and Rainer Schneider Center of Molecular Biosciences (CMBI), Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria The neuronal proteins GAP43 (neuromodulin), MARCKS, and BASP1 are highly expressed in the growth cones of nerve cells where they are involved in signal transmission and cytoskeleton organization. Although their primary structures are unrelated, these signaling proteins share several structural properties like fatty acid modification, and the presence of cationic effector domains. GAP43, MARCKS, and BASP1 bind to cell membrane phospholipids, a process reversibly regulate...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions: These finding suggest that Poly-ICLC could be safely used for inducing transient innate immune responses in treated HIV+ subjects indicating promise as an adjuvant for HIV therapeutic vaccines. Trial Registration: www.ClinicalTrials.gov, identifier: NCT02071095. Introduction Innate immune dysregulation during HIV infection hinders the formation of anti-HIV adaptive immunity (1–6) resulting in rampant viral dissemination and progression to AIDS. Adherence to combination anti-retroviral therapy (cART) regimens controls viremia, restores CD4+T cell counts and reverses immune dysfunction to a larg ext...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
In conclusion, eculizumab is the first disease-modifying, targeted therapy for PNH and its availability has radically changed the management of patients with this rare disease.DisclosuresYenerel: Alexion: Honoraria, Speakers Bureau.
Source: Blood - Category: Hematology Authors: Tags: 101. Red Cells and Erythropoiesis, Structure and Function, Metabolism, and Survival, Excluding Iron Source Type: research
This study, the largest series of infection in MDS patients, seeks to comprehensively analyse infection in this cohort.Method: CT scan, microbiology results and hospital admission ICD codes from January 1999 to April 2017 were analysed for 657 MDS patients enrolled in the South Australian MDS (SA-MDS) registry. Cox regression analysis was performed to ascertain risk factors for developing infection.Results: There were 531 primary and 126 therapy-related myeloid neoplasm (t-MN) patients with median age of 69.2 (18-97) years. According to Revised International Prognostic Scoring System (IPSS-R), 44.7% of patients were classi...
Source: Blood - Category: Hematology Authors: Tags: 637. Myelodysplastic Syndromes-Clinical Studies: Poster I Source Type: research
Conclusions. APAVAC is a simple method for AV with high clinical impact in very bad situations. It could be used in combination with other therapy and for residual disease control. Further clinical studies are planned in solid C as well as in HM.DisclosuresRouquet: URODELIA: Employment. Frayssinet: URODELIA: Employment.
Source: Blood - Category: Hematology Authors: Tags: 703. Adoptive Immunotherapy Source Type: research
AbstractThe myelodysplastic syndromes, the chronic myeloproliferative neoplasms, and the acute myeloid leukemia are malignancies of the myeloid hematopoietic stem cells of the bone marrow. The diseases are characterized by a dysregulation of the immune system as both the cytokine milieu, immune phenotype, immune regulation, and expression of genes related to immune cell functions are deregulated. Several treatment strategies try to circumvent this deregulation, and several clinical and preclinical trials have shown promising results, albeit not in the same scale as chimeric antigen receptor T cells have had in the treatmen...
Source: Seminars in Immunopathology - Category: Pathology Source Type: research
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]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
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...
Source: Blood - Category: Hematology Authors: Tags: Immunobiology and Immunotherapy, Myeloid Neoplasia, Clinical Trials and Observations, Gene Therapy Source Type: research
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
Source: Cancer Science - Category: Cancer & Oncology Authors: Tags: Original Article Source Type: research
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]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
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