Analogue peptides for the immunotherapy of human acute myeloid leukemia

Hofmann, Susanne; Mead, Andrew; Malinovskis, Aleksandrs; Hardwick, Nicola; Guinn, Barbara

doi:10.1007/s00262-015-1762-9

Cited by 10 publications

(7 citation statements)

References 98 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Intriguingly, we found that short sequences of four aminoacids from the C-terminal of the NPM1-mutated protein, namely LCLA, CLAV, LAVE, SLRK and VEEV, are homologous with many common bacterial and viral antigens (not shown), suggesting possible cross-reactive immune response mechanisms, as previously documented in melanoma. [20, 21]. This observation may account for the broad immune responses observed in our patients, and may also explain the absence of a significant difference in the levels of these responses in peripheral blood according to age, as the elderly patients in our cohort displayed high levels of antiviral T-cell responses.…”

Section: Discussionmentioning

confidence: 52%

Characterization and dynamics of specific T cells against nucleophosmin-1 (NPM1)-mutated peptides in patients with NPM1-mutated acute myeloid leukemia

et al. 2019

View full text Add to dashboard Cite

Nucleophosmin(NPM1)-mutated protein, a leukemia-specific antigen, represents an ideal target for AML immunotherapy. We investigated the dynamics of NPM1-mutated-specific T cells on PB and BM samples, collected from 31 adult NPM1-mutated AML patients throughout the disease course, and stimulated with mixtures of 18 short and long peptides (9-18mers), deriving from the complete C-terminal of the NPM1-mutated protein. Two 9-mer peptides, namely LAVEEVSLR and AVEEVSLRK (13.9–14.9), were identified as the most immunogenic epitopes. IFNγ-producing NPM1-mutated-specific T cells were observed by ELISPOT assay after stimulation with peptides 13.9–14.9 in 43/85 (50.6%) PB and 34/80 (42.5%) BM samples. An inverse correlation between MRD kinetics and anti-leukemic specific T cells was observed. Cytokine Secretion Assays allowed to predominantly and respectively identify Effector Memory and Central Memory T cells among IFNγ–producing and IL2–producing T cells. Moreover, NPM1-mutated-specific CTLs against primary leukemic blasts or PHA-blasts pulsed with different peptide pools could be expanded ex vivo from NPM1-mutated AML patients or primed in healthy donors. We describe the spontaneous appearance and persistence of NPM1-mutated-specific T cells, which may contribute to the maintenance of long-lasting remissions. Future studies are warranted to investigate the potential role of both autologous and allogeneic adoptive immunotherapy in NPM1-mutated AML patients.

show abstract

Section: Discussionmentioning

confidence: 52%

Characterization and dynamics of specific T cells against nucleophosmin-1 (NPM1)-mutated peptides in patients with NPM1-mutated acute myeloid leukemia

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Both autoreactive immune cells and their secreted cytokines can result in harmful autoreactive immune attacks towards host cells and tissues, and thus, they are the two main targets for immunotherapy in rheumatic diseases. Distinct forms of peptide-based vaccinations have been studied for therapeutic or preventive strategies for diseases such as cancer, rheumatic diseases, and allergic disorders [34][35][36][37][38]. According to the therapeutic targets, peptide-based vaccinations used for rheumatic diseases can be classified into two main subtypes including peptide-based active vaccination against pathogenic cytokines and peptide-based tolerogenic vaccination.…”

Section: Types Of Peptide-based Vaccination Therapymentioning

confidence: 99%

“…Many peptide autoepitopes have been proven to be involved in the pathogenesis of SLE [167][168][169]. Some histone peptides such as histone H4 autoepitope peptide 16-39 (H4 ) and autoepitope peptide 71-94 (H4 ) could induce an inflammatory response, whereas others such as H2A [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] could lead to an immunosuppressive response [167,168]. Therefore, different peptides can lead to distinct immune response during the development of SLE.…”

Section: Journal Of Immunology Researchmentioning

confidence: 99%

Peptide-Based Vaccination Therapy for Rheumatic Diseases

Wang

Chen

Zheng

et al. 2020

Journal of Immunology Research

View full text Add to dashboard Cite

Rheumatic diseases are extremely heterogeneous diseases with substantial risks of morbidity and mortality, and there is a pressing need in developing more safe and cost-effective treatment strategies. Peptide-based vaccination is a highly desirable strategy in treating noninfection diseases, such as cancer and autoimmune diseases, and has gained increasing attentions. This review is aimed at providing a brief overview of the recent advances in peptide-based vaccination therapy for rheumatic diseases. Tremendous efforts have been made to develop effective peptide-based vaccinations against rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), while studies in other rheumatic diseases are still limited. Peptide-based active vaccination against pathogenic cytokines such as TNF-α and interferon-α (IFN-α) is shown to be promising in treating RA or SLE. Moreover, peptide-based tolerogenic vaccinations also have encouraging results in treating RA or SLE. However, most studies available now have been mainly based on animal models, while evidence from clinical studies is still lacking. The translation of these advances from experimental studies into clinical therapy remains impeded by some obstacles such as species difference in immunity, disease heterogeneity, and lack of safe delivery carriers or adjuvants. Nevertheless, advances in high-throughput technology, bioinformatics, and nanotechnology may help overcome these impediments and facilitate the successful development of peptide-based vaccination therapy for rheumatic diseases.

show abstract

“…In some instances replacement of amino acids at the anchor residues increases the binding of peptide to MHC followed by the increased chance of TCR stimulation [33]. The length of peptide can also be important to achieve effective CD8 responses.…”

Section: Issues Related To the Selection And Delivery Of Peptide Vaccmentioning

confidence: 99%

Peptide vaccines in cancer — old concept revisited

Kumai

Kobayashi

Harabuchi

et al. 2017

Current Opinion in Immunology

View full text Add to dashboard Cite

Synthetic peptide vaccines aim to elicit and expand tumor-specific T cells capable of controlling or eradicating the tumor. Despite the high expectations based on preclinical studies, the results of clinical trials using peptide vaccines have been disappointing. Thus, many researchers in the field have considered peptide vaccines as outdated and no longer viable for cancer therapy. However, recent progress in understanding the critical roles of immune adjuvants, modes of vaccine administration and T cell dynamics has lead to a rebirth of this approach and reconsidering the use of peptide vaccines for treating malignant disorders.

show abstract

Analogue peptides for the immunotherapy of human acute myeloid leukemia

Cited by 10 publications

References 98 publications

Characterization and dynamics of specific T cells against nucleophosmin-1 (NPM1)-mutated peptides in patients with NPM1-mutated acute myeloid leukemia

Characterization and dynamics of specific T cells against nucleophosmin-1 (NPM1)-mutated peptides in patients with NPM1-mutated acute myeloid leukemia

Peptide-Based Vaccination Therapy for Rheumatic Diseases

Peptide vaccines in cancer — old concept revisited

Contact Info

Product

Resources

About