Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia

Maslak, P.; Dao, Tao; Bernal, Yvette; Chanel, Suzanne; Zhang, Rong; Frattini, Mark G.; Rosenblat, Todd L.; Jurcic, Joseph G.; Brentjens, Renier J.; Arcila, Maria E.; Rampal, Raajit K.; Park, Jae H.; Douer, Dan; Katz, Laura M.; Sarlis, Nicholas J.; Tallman, Martin S.; Scheinberg, David A.

doi:10.1182/bloodadvances.2017014175

Cited by 131 publications

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“…Another example is between WT1 and HLA-B . The WT1 protein has been chosen as an immunologic target by a National Cancer Institute initiative [46], and this year, a phase 2 clinical trial showed a WT1 vaccine that is effective in Acute Myeloid Leukemia with predicted binding on HLA-B*15:01, HLA-B*39:01, HLA-B*07:02, and HLA-B*08, HLA-B27:05 in addition to HLA-A*02 [47]. These MeTeOR predictions suggests that further investigation is warranted and highlights the ability of the network to suggest complex gene–disease–gene relationships.…”

Section: Resultsmentioning

confidence: 99%

Automated literature mining and hypothesis generation through a network of Medical Subject Headings

Wilson

et al. 2018

Preprint

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25 The scientific literature is vast, growing, and increasingly specialized, making it difficult to 26 connect disparate observations across subfields. To address this problem, we sought to develop 27 automated hypothesis generation by networking at scale the MeSH terms curated by the National 28 Library of Medicine. The result is a Mesh Term Objective Reasoning (MeTeOR) approach that 29 tallies associations among genes, drugs and diseases from PubMed and predicts new ones.30 Comparisons to reference databases and algorithms show MeTeOR tends to be more reliable. We 31 also show that many predictions based on the literature prior to 2014 were published 32 subsequently. In a practical application, we validated experimentally a surprising new 33 association found by MeTeOR between novel Epidermal Growth Factor Receptor (EGFR) 34 associations and CDK2. We conclude that MeTeOR generates useful hypotheses from the 35 literature (http://meteor.lichtargelab.org/). AUTHOR SUMMARY37 The large size and exponential expansion of the scientific literature forms a bottleneck to 38 accessing and understanding published findings. Manual curation and Natural Language 39 Processing (NLP) aim to address this bottleneck by summarizing and disseminating the 40 knowledge within articles as key relationships (e.g. TP53 relates to Cancer). However, these 41 methods compromise on either coverage or accuracy, respectively. To mitigate this compromise, 42 we proposed using manually-assigned keywords (MeSH terms) to extract relationships from the 43 publications and demonstrated a comparable coverage but higher accuracy than current NLP 44 methods. Furthermore, we combined the extracted knowledge with semi-supervised machine 45 learning to create hypotheses to guide future work and discovered a direct interaction between 46 two important cancer genes. 47 48 49 3 50 INTRODUCTION 51 It is difficult to keep abreast of new publications. Currently, PubMed contains over 28 million 52 papers (http://www.ncbi.nlm.nih.gov/pubmed)-3 million more than three years ago. This steady 53 accumulation of findings gives rise to a large number of latent connections that Literature-Based 54 Discovery (LBD) seeks to systematically recognize and integrate [1], such as Swanson's original 55 finding linking fish oil to the treatment of Raynaud's disease [2]. Since this original analysis, 56 LBD has been extensively replicated, automated and expanded [3-10], leading to new patterns of 57 inference -e.g. locating opposing actions of a disease and a drug on given physiological 58 functions [11] -and to new discoveries [12]. Successes include the automated discovery of 59 protein functions [13, 14] and of the genetic bases of disease [15, 16], as well as the stratification 60 of patient phenotypes [17] and outcomes [18]. 61A limitation of LBD, however, is its dependence on knowledge extraction. It either relies 62 on human curation, which is not scalable, or on comprehensive text-mining, for which 63 algorithms are less accurate [19, 20]. One of the largest curated m...

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Section: Resultsmentioning

confidence: 99%

Automated literature mining and hypothesis generation through a network of Medical Subject Headings

Wilson

et al. 2018

Preprint

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“…antigens such as SLAMF7, CD38, CD74, or CD138 39 , providing naturally processed HLA-presented ligands derived from intracellular domains of established membrane-bound tumor-associated antigens. Such HLA ligands represent promising targets for (i) low side effect single agent vaccine approaches in elderly patients or early disease states 21,28,40 , (ii) TCR-engineered T cells 41 , (iii) antibody-based approaches 42 , or (iv) novel approaches combining HLA-dependent and -independent antigens and treatments 43 . In addition, such T-cell epitopes can be used for the assessment and monitoring of T-cell responses following various types of antigen-specific, or as in this example BCMA-specific, immunotherapy approaches.…”

Section: Discussionmentioning

confidence: 99%

Mass spectrometry-based identification of a B-cell maturation antigen-derived T-cell epitope for antigen-specific immunotherapy of multiple myeloma

et al. 2020

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The B-cell maturation antigen (BCMA) is currently being evaluated as promising tumor-associated surface antigen for T-cell-based immunotherapy approaches, such as CAR T cells and bispecific antibodies, in multiple myeloma (MM). Cytotoxic T cells bearing BCMA-specific T-cell receptors might further allow targeting HLA-presented antigens derived from the intracellular domain of BCMA. By analyzing a mass spectrometry-acquired immunopeptidome dataset of primary MM samples and MM cell lines for BCMA-derived HLA ligands, we identified the naturally presented HLA-B*18restricted ligand P(BCMA) B*18. Additionally, P(BCMA) B*18 was identified on primary CLL samples, thereby expanding the range for possible applications. P(BCMA) B*18 induced multifunctional BCMA-specific cells de novo from naïve CD8 + T cells of healthy volunteers. These T cells exhibited antigen-specific lysis of autologous peptide-loaded cells. Even in the immunosuppressive context of MM, we detected spontaneous memory T-cell responses against P(BCMA) B*18 in patients. By applying CTLA-4 and PD-1 inhibition in vitro we induced multifunctional P(BCMA) B*18-specific CD8 + T cells in MM patients lacking preexisting BCMA-directed immune responses. Finally, we could show antigen-specific lysis of autologous peptide-loaded target cells and even MM.1S cells naturally presenting P(BCMA) B*18 using patient-derived P(BCMA) B*18-specific T cells. Hence, this BCMA-derived T-cell epitope represents a promising target for T-cell-based immunotherapy and monitoring following immunotherapy in B-cell malignancy patients.

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“…The peptide vaccine is often synthetic and mimics naturally occurring proteins from pathogens and these peptides based vaccine have shown promising successful results in the past for disease like malaria, dengue, multiple sclerosis, influenza. Besides of these diseases, peptide based vaccines have also been developed against several types of cancer like colorectal cancer, myeloid leukaemia and gastric cancer (47),(48),(49). The identification and design of immunogenic peptides (epitopes) is expensive as well as time consuming.…”

Section: Discussionmentioning

confidence: 99%

Design of an Epitope-Based Peptide Vaccine against the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): A Vaccine-informatics Approach

Khan

Alam²,

Imam

et al. 2020

Preprint

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The recurrent and recent global outbreak of SARS-COV-2 has turned into a global concern which has infected more than one million people all over the globe, and this number is increasing in hours. Unfortunate no vaccine or specific treatment is available, which make it more deadly.An immunoinformatics approach has shown significant breakthrough in peptide-based epitope mapping and opens the new horizon in vaccine development. In this study, we have identified a total of 15 antigenic peptides (including T and B Cells) in the surface glycoprotein of SARS-CoV-2 which found to be 100% conserved with other SARS coronaviruses. Furthermore, the population coverage analysis has found that CD4 + T-cell peptides showed higher cumulative population coverage over to CD8 + peptides in the 16 different geographical regions in the world. Notably, only 09 out of 15 peptides (LTDEMIAQY, IRASANLAA, FGAISSVLN, VKQLSSNFG, FAMQMAYRF, FGAGAALQ, VITPGTNTS, WTAGAAAYY and QTQTNSPRRARS) that have 8 0 % െ 9 0 % identity with experimentally identified epitopes of different organisms including SARS-CoV and this will likely be beneficial for a quick progression of the vaccine design. Moreover, docking analysis suggested that these peptides are tightly bound in the groove of HLA molecules which can induce the T-cell response. Overall this study allows us to determine potent peptide antigen targets in surface glycoprotein on intuitive grounds which open up a new horizon in COVID-19 research. However, this study needs experimental validation by in vitro and in vivo. low affinity)(16). We chose those peptides (epitopes) only which have binding affinity 4 0 0 ݊ ݉ for the further analysis. Next, we check the probability of selected peptides for naturally processed and tied with MHC molecule by using MHC-NP tool(20).

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Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia

Abstract: Key Points A heteroclitic WT1 peptide vaccine is well tolerated and induces immunologic responses in most acute myeloid leukemia patients post-CR1. Median overall survival for the group of patients vaccinated was not reached but is poised to reach or exceed 67.6 months.

Cited by 131 publications

References 44 publications

Automated literature mining and hypothesis generation through a network of Medical Subject Headings

Automated literature mining and hypothesis generation through a network of Medical Subject Headings

Mass spectrometry-based identification of a B-cell maturation antigen-derived T-cell epitope for antigen-specific immunotherapy of multiple myeloma

Design of an Epitope-Based Peptide Vaccine against the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): A Vaccine-informatics Approach

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