ArticleCancer immunology, immunotherapy : CII2022
Epigenetic therapy in combination with a multi-epitope cancer vaccine targeting shared tumor antigens for high-risk myelodysplastic syndrome - a phase I clinical trial.
Article in Cancer immunology, immunotherapy : CII, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Innovative combinatory approaches with dendritic cell-based vaccines: bridging preclinical insights and clinical challenges.Clinical and experimental medicine · 2026Review
- Article
- Wilms' tumor 1 -targeting cancer vaccine: Recent advancements and future perspectives.Human vaccines & immunotherapeutics · 2024Review
- mRNA vaccines as cancer therapies.Chinese medical journal · 2024Review
- Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation.Molecular cancer · 2023Review
- Article
- Targeting DNA Methylation in Leukemia, Myelodysplastic Syndrome, and Lymphoma: A Potential Diagnostic, Prognostic, and Therapeutic Tool.International journal of molecular sciences · 2022Review
- Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1): A Promising Cancer Testis Antigen.Aging and disease · 2022Review
- Epi-immunotherapy for cancers: rationales of epi-drugs in combination with immunotherapy and advances in clinical trials.Cancer communications (London, England) · 2022Review
- Exploring glioblastoma stem cell heterogeneity: Immune microenvironment modulation and therapeutic opportunities.Frontiers in oncology · 2022Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundStandard care for patients with high-risk myelodysplastic syndrome (MDS) is hypomethylating agents such as azacitidine (AZA), which can induce expression of methylated tumor-associated antigens and therefore potentiate immunotherapeutic targeting.
methodIn this phase 1 trial, we combined AZA with a therapeutic peptide vaccine targeting antigens encoded from NY-ESO-1, MAGE-A3, PRAME, and WT-1, which have previously been demonstrated to be upregulated by AZA treatment.
resultFive patients who had responded to AZA monotherapy were included in the study and treated with the vaccine. The combination therapy showed only few adverse events during the study period, whereof none classified as serious. However, no specific immune responses could be detected using intracellular cytokine staining or ELISpot assays. Minor changes in the phenotypic composition of immune cells and their expression of stimulatory and inhibitory markers were detected. All patients progressed to AML with a mean time to progression from inclusion (TTP) of 5.2 months (range 2.8 to 7.6). Mean survival was 18.1 months (range 10.9 to 30.6) from MDS diagnosis and 11.3 months (range 4.3 to 22.2) from inclusion. Sequencing of bone marrow showed clonal expansion of malignant cells, as well as appearance of novel mutations.
conclusionThe patients progressed to AML with an average time of only five months after initiating the combination therapy. This may be unrelated to the experimental treatment, but the trial was terminated early as there was no sign of clinical benefit or immunological response. Why the manuscript is especially interesting This study is the first to exploit the potential synergistic effects of combining a multi-peptide cancer vaccine with epigenetic therapy in MDS. Although our results are negative, they emphasize challenges to induce immune reactivity in patients with high-risk MDS.
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