Strategy for Designing a Synthetic Tumor Vaccine:  Multi-Component, Multivalency and Antigen Modification

Huang, Zhihua; Sun, Zhongyang; Gao, Yue; Chen, Pu‐Guang; Liu, Yanfang; Chen, Yong-Xiang; Li, Yanmei

doi:10.3390/vaccines2030549

Cited by 9 publications

(11 citation statements)

References 81 publications

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“…It was found that, in preclinical study, anti‐Tn titers of Rha‐YAF‐Tn were higher when preimmunized with Rha‐OVA in mice, confirming the important role of the Rha in mediating the immune response . Li and co‐workers also synthesized several vaccine candidates containing MUC1 glycopeptides as the B‐cell epitopes, a T‐cell epitope peptide, and the Pam3CSK4 as TLR agonist . Recently, Guo and co‐workers synthesized a two‐component cancer vaccine candidate containing STn and αGalCer since αGalCer can play several roles such as liposomal carrier vehicle, activation of APCs, and Th epitope‐like function.…”

Section: Advances In Tacas Based Cancer Vaccinesmentioning

confidence: 94%

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Carbohydrate‐based vaccines for oncotherapy

Wei

Wang

2018

Medicinal Research Reviews

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Cancer is still one of the most serious threats to human worldwide. Aberrant patterns of glycosylation on the surface of cancer cells, which are correlated with various cancer development stages, can differentiate the abnormal tissues from the healthy ones. Therefore, tumor-associated carbohydrate antigens (TACAs) represent the desired targets for cancer immunotherapy. However, these carbohydrate antigens may not able to evoke powerful immune response to combat with cancer for their poor immunogenicity and immunotolerance. Different approaches have been developed to address these problems. In this review, we want to summarize the latest advances in TACAs based anticancer vaccines.

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Section: Advances In Tacas Based Cancer Vaccinesmentioning

confidence: 94%

“…132 Li and co-workers also synthesized several vaccine candidates containing MUC1 glycopeptides as the B-cell epitopes, a T-cell epitope peptide, and the Pam3CSK4 as TLR agonist. 133,134 Recently, Guo and co-workers 135…”

Section: Th Cell Epitope Is Another Common Component For Improving Thmentioning

confidence: 99%

Carbohydrate‐based vaccines for oncotherapy

Wei

Wang

2018

Medicinal Research Reviews

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“…Human MUC1 glycoproteins with abnormal O‐glycans have been found in high abundance on surfaces of epithelial tumor cells and have been investigated as potential candidates for antitumor vaccines. Prior investigations suggest that the presentation of MUC1 directly impacts immunogenicity, e.g., MUC1 fibrils led to effective B‐cell responses, while soluble monomeric MUC1 molecules exhibited little immunogenicity . Therefore, the effective molecule is MUC1 conjugated with an eleven residue long Q11 peptide, as shown in Figure .…”

Section: Introductionmentioning

confidence: 99%

Local Mechanical Perturbation Provides an Effective Means to Regulate the Growth and Assembly of Functional Peptide Fibrils

Karsai

Slack

Malekan

et al. 2016

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Mucin 1 (MUC1) peptide fused with Q11 (MUC1-Q11) having 35 residues has previously been shown to form amyloid fibrils. Using time-dependent and high-resolution atomic force microscopy (AFM) imaging, it is revealed that the formation of individual MUC1-Q11 fibrils entails nucleation and extension at both ends. This process can be altered by local mechanical perturbations using AFM probes. This work reports two specific perturbations and outcomes. First, by increasing load while maintaining tip-surface contact, the fibrils are cut during the scan due to shearing. Growth of fibrils occurs at the newly exposed termini, following similar mechanism of the MUC1-Q11 nucleation growth. As a result, branched fibrils are seen on the surface whose orientation and length can be controlled by the nuclei orientation and reaction time. In contrast to the "one-time-cut", fibrils can be continuously fragmented by modulation at sufficiently high amplitude. As a result, short and highly branched fibrils accumulate and pile on surfaces. Since the fibril formation and assembly of MUC1-Q11 can be impacted by local mechanical force, this approach offers a nonchemical and label-free means to control the presentation of MUC1 epitopes, and has promising application in MUC1 fibril-based immunotherapy.

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“…Despite encouraging results in some clinical trials, cancer vaccines are yet to have an impact on cancer [ 1 , 2 ]. Many strategies specific for a particular tumour associated antigen (TAA), including single or multiple peptides with or without ex vivo dendritic cells (DC) pulsing, DC targeting immunogens with or without adjuvants such as a toll-like receptor (TLR) agonist have been used [ 2 , 3 , 4 , 5 , 6 ]. To overcome some of the limitations of previous peptide vaccine strategies it is necessary to (1) incorporate both CD8 cytotoxic T cell (Tc) and CD4 T helper cell (Th) epitopes to promote the generation of long term immunity; (2) MHC restriction must be considered to allow application to the wider population and; (3) consideration to the most effective adjuvant to enhance immunogenicity [ 7 , 8 , 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity of a Tripartite Cell Penetrating Peptide Containing a MUC1 Variable Number of Tandem Repeat (VNTR) and A T Helper Epitope

et al. 2018

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Peptide-based vaccines for cancer have many advantages however, for optimization these immunogens should incorporate peptide epitopes that induce CD8, as well as CD4 responses, antibody and long term immunity. Cell penetrating peptides (CPP) with a capacity of cytosolic delivery have been used to deliver antigenic peptides and proteins to antigen presenting cells to induce cytotoxic T cell, helper T cell and humoral responses in mice. For this study, a tripartite CPP including a mucin 1 (MUC1) variable number of tandem repeat (VNTR) containing multiple T cell epitopes and tetanus toxoid universal T helper epitope peptide (tetCD4) was synthesised (AntpMAPMUC1tet) and immune responses investigated in mice. Mice vaccinated with AntpMAPMUC1tet + CpG show enhanced antigen-specific interferon-gamma (IFN-γ) and IL-4 T cell responses compared with AntpMAPMUC1tet vaccination alone and induced a Th1 response, characterised by a higher ratio of IgG2a antibody/IgG1 antibodies. Furthermore, vaccination generated long term MUC1-specific antibody and T cell responses and delayed growth of MUC1+ve tumours in mice. This data demonstrates the efficient delivery of branched multiple antigen peptides incorporating CPP and that the addition of CpG augments immune responses.

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Strategy for Designing a Synthetic Tumor Vaccine: Multi-Component, Multivalency and Antigen Modification

Cited by 9 publications

References 81 publications

Carbohydrate‐based vaccines for oncotherapy

Carbohydrate‐based vaccines for oncotherapy

Local Mechanical Perturbation Provides an Effective Means to Regulate the Growth and Assembly of Functional Peptide Fibrils

Immunogenicity of a Tripartite Cell Penetrating Peptide Containing a MUC1 Variable Number of Tandem Repeat (VNTR) and A T Helper Epitope

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