Mechanistic insights into the efficacy of cell penetrating peptide-based cancer vaccines

Grau, Morgan; Walker, Paul R; Derouazi, Madiha

doi:10.1007/s00018-018-2785-0

Cited by 37 publications

(40 citation statements)

References 82 publications

(111 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In general, CPPs were used to deliver antigenic peptides or proteins, induce adaptive immune responses and activate both CD8 + and CD4 + T cells [283]. For example, the EBV ZEBRA proteinderived CPPs (Z12, Z13, or Z14) linked to antigenic cargos (e.g.…”

Section: Vaccinementioning

confidence: 99%

See 1 more Smart Citation

Cell penetrating peptides: the potent multi-cargo intracellular carriers

Kardani

Milani

Shabani

et al. 2019

Expert Opinion on Drug Delivery

143

View full text Add to dashboard Cite

Introduction: Cell penetrating peptides (CPPs) known as protein translocation domains (PTD), membrane translocating sequences (MTS), or Trojan peptides (TP) are able to cross biological membranes without clear toxicity using different mechanisms, and facilitate the intracellular delivery of a variety of bioactive cargos. CPPs could overcome some limitations of drug delivery and combat resistant strains against a broad range of diseases. Despite delivery of different therapeutic molecules by CPPs, they lack cell specificity and have a short duration of action. These limitations led to design of combined cargo delivery systems and subsequently improvement of their clinical applications. Areas covered: This review covers all our studies and other researchers in different aspects of CPPs such as classification, uptake mechanisms, and biomedical applications. Expert opinion: Due to low cytotoxicity of CPPs as compared to other carriers and final degradation to amino acids, they are suitable for preclinical and clinical studies. Generally, the efficiency of CPPs was suitable to penetrate the cell membrane and deliver different cargos to specific intracellular sites. However, no CPP-based therapeutic approach has approved by FDA, yet; because there are some disadvantages for CPPs including short half-life in blood, and nonspecific CPP-mediated delivery to normal tissue. Thus, some methods were used to develop the functions of CPPs in vitro and in vivo including the augmentation of cell specificity by activatable CPPs, specific transport into cell organelles by insertion of corresponding localization sequences, incorporation of CPPs into multifunctional dendrimeric or liposomal nanocarriers to improve selectivity and efficiency especially in tumor cells.

show abstract

Section: Vaccinementioning

confidence: 99%

“…Increased antigen (Ag)-specific immune responses were also reported by linking other tumor antigens (e.g. carcinoembryonic antigen, TRP2, survivin, p53, HPV16 E7, MUC-1, or HER2/neu) to a CPP [283]. Wang et al demonstrated that the linkage of TRP2 Ag to CPPs could prolong antigen presentation by dendritic cells (DCs) [286].…”

Section: Vaccinementioning

confidence: 99%

Cell penetrating peptides: the potent multi-cargo intracellular carriers

Kardani

Milani

Shabani

et al. 2019

Expert Opinion on Drug Delivery

143

View full text Add to dashboard Cite

show abstract

“…The ability of a given substance to trigger an immune response is referred to as immunogenicity (6, 8). In a broader sense, immunogenicity refers to the activation of both sides of adaptive immunity: cellular response (mediated by cytotoxic cells) and humoral response (mediated by antibodies).…”

Section: Introductionmentioning

confidence: 99%

“…In a broader sense, immunogenicity refers to the activation of both sides of adaptive immunity: cellular response (mediated by cytotoxic cells) and humoral response (mediated by antibodies). The activation of T-cells is a decisive step in both cases (8, 9), and it will also be referred to as immunogenicity here. T-cells are a special type of lymphocyte that undergo a complex maturation and selection process, which makes them capable of recognizing “non-self” peptides (10).…”

Section: Introductionmentioning

confidence: 99%

Structure-based Methods for Binding Mode and Binding Affinity Prediction for Peptide-MHC Complexes

Antunes

Abella

Devaurs

et al. 2019

CTMC

View full text Add to dashboard Cite

Understanding the mechanisms involved in the activation of an immune response is essential to many fields in human health, including vaccine development and personalized cancer immunotherapy. A central step in the activation of the adaptive immune response is the recognition, by T-cell lymphocytes, of peptides displayed by a special type of receptor known as Major Histocompatibility Complex (MHC). Considering the key role of MHC receptors in T-cell activation, the computational prediction of peptide binding to MHC has been an important goal for many immunological applications. Sequence-based methods have become the gold standard for peptide-MHC binding affinity prediction, but structure-based methods are expected to provide more general predictions (i.e., predictions applicable to all types of MHC receptors). In addition, structural modeling of peptide-MHC complexes has the potential to uncover yet unknown drivers of T-cell activation, thus allowing for the development of better and safer therapies. In this review, we discuss the use of computational methods for the structural modeling of peptide-MHC complexes (i.e., binding mode prediction) and for the structure-based prediction of binding affinity.

show abstract

“…The cell penetrating property of these peptides have been utilized to deliver antigenic peptide and proteins into any antigen presenting cell including DCs for the development of vaccine delivery systems [ 4 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. For this purpose, CPP peptides chemically conjugated to protein antigens or linear synthetic peptides of CPP fused in tandem with cytotoxic (Tc) or helper (Th) T cell epitopes have been used.…”

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

View full text Add to dashboard Cite

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.

show abstract

Mechanistic insights into the efficacy of cell penetrating peptide-based cancer vaccines

Cited by 37 publications

References 82 publications

Cell penetrating peptides: the potent multi-cargo intracellular carriers

Cell penetrating peptides: the potent multi-cargo intracellular carriers

Structure-based Methods for Binding Mode and Binding Affinity Prediction for Peptide-MHC Complexes

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

Contact Info

Product

Resources

About