The translocation motif of hepatitis B virus improves protein vaccination

Bleifuß, Elke; Kammertoens, Thomas; Hutloff, Andreas; Quarcoo, David; Dorner, Martin B.; Straub, P W; Uckert, Wolfgang; Hildt, Eberhard

doi:10.1007/s00018-005-5548-7

Cited by 29 publications

(21 citation statements)

References 30 publications

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“…or s.c.) to maximize the probability of targeting DCs. This route of administration of CPP-based cancer vaccines has been proven to be efficacious, as revealed by strong Ag-specific T-cell responses elicited against various Ag [21, 24, 47, 72]. An elegant study of Zhang et al clearly showed that s.c. administration of a CPP-based vaccine efficiently triggers peripheral DCs [27].…”

Section: Route Of Administration Of Cpp-based Cancer Vaccinesmentioning

confidence: 99%

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

Grau¹,

Walker

Derouazi³

2018

Cell. Mol. Life Sci.

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Immunotherapies are increasingly used to treat cancer, with some outstanding results. Immunotherapy modalities include therapeutic vaccination to eliminate cancer cells through the activation of patient’s immune system against tumor-derived antigens. Nevertheless, the full potential of therapeutic vaccination has yet to be demonstrated clinically because many early generation vaccines elicited low-level immune responses targeting only few tumor antigens. Cell penetrating peptides (CPPs) are highly promising tools to advance the field towards clinical success. CPPs efficiently penetrate cell membranes, even when linked to antigenic cargos, which can induce both CD8 and CD4 T-cell responses. Pre-clinical studies demonstrated that targeting multiple tumor antigens, even those considered to be poorly immunogenic, led to tumor regression. Therefore, CPP-based cancer vaccines represent a flexible and powerful means to extend therapeutic vaccination to many cancer indications. Here, we review recent findings in CPP development and discuss their use in next generation immunotherapies.

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Section: Route Of Administration Of Cpp-based Cancer Vaccinesmentioning

confidence: 99%

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

Grau¹,

Walker

Derouazi³

2018

Cell. Mol. Life Sci.

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“…The fourth class of CPPs are peptides derived from hydrophobic sequences of proteins which naturally interact with plasma membrane, e.g. integrin b3-fragment [16], Hepatitis B virus translocation motif [17] or calcitonin fragment (Table 1) [18].…”

Section: Cpp Classificationmentioning

confidence: 99%

Cell-penetrating peptides as a promising tool for delivery of various molecules into the cells

Ruczyński

Wierzbicki²,

Kogut-Wierzbicka³

et al. 2015

Folia Histochem Cytobiol.

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Many biologically active compounds, including macromolecules that are used as various kinds of drugs, must be delivered to the interior of cell or organelles such as mitochondria or nuclei to achieve a therapeutic effect. However, very often, lipophilic cell membrane is impermeable for these molecules. A new method in the transport of macromolecules through the cell membrane is the one based on utilizing cell-penetrating peptides (CPPs). Invented 25 years ago, CPPs are currently the subject of intensive research in many laboratories all over the world. CPPs are short compounds comprising up to 30 amino acid residues, which penetrate the cell membrane but do not cause cell damage. Additionally, CPPs can transfer hydrophilic molecules (peptides, proteins, nucleic acids) which exceed their mass, and for which the cell membrane is generally impermeable. In this review, we concentrate on the cellular uptake mechanism of CPPs and a method of conjunction of CPPs to the transported molecules. We also highlight the potential of CPPs in delivering various kinds of macromolecules into cells, including compounds of therapeutic interest.

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“…Thus, we next evaluated the amplitude and nature of the humoral and cell-mediated immunity developed in vivo in response to both prophylactic and therapeutic vaccines in nicotine-exposed mice. We implemented the OVA-EG7 immunogenic tumor model (31) used by others in preclinical studies testing vaccine formulation for cancer and infections (32)(33)(34)(35)(36)(37)(38)(39). To study the effects of nicotine on prophylactic vaccination, WT C57BL/6 mice were implanted with osmotic pumps containing nicotine and then were vaccinated twice s.c. at the base of the tail with OVA protein mixed with the Th1 adjuvants LPS or CpG.…”

Section: Nicotine Exposure Compromises the Effectiveness Of Both Propmentioning

confidence: 99%

Exposure to Nicotine Adversely Affects the Dendritic Cell System and Compromises Host Response to Vaccination

Nouri-Shirazi

Guinet

2012

The Journal of Immunology

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The magnitude of Th1 cells response to vaccination is a critical factor in determining protection from clinical disease. Our previous in vitro studies suggested that exposure to the nicotine component of cigarette smoke skews the differentiation of both human and mouse dendritic cell (DC) precursors into atypical DCs (DCs differentiated ex vivo in the presence of nicotine) lacking parameters essential for the development of Th1-mediated immunity. In this study, we determined the causal relationship between nicotine-induced DC alterations and host response to vaccines. We show that animals exposed to nicotine failed to develop and maintain Ag-specific effector memory Th1 cells and Ab production to protein-based vaccine formulated with Th1 adjuvants. Accordingly, both prophylactic and therapeutic vaccines failed to protect and cure the nicotine-exposed mice from disease. More importantly, we demonstrate the nicotine-induced defects in the biological activities of in vivo DCs as an underlying mechanism. Indeed, i.v. administration of DCs differentiated in the presence of nicotine preferentially promoted the development of Ag-specific IL-4–producing effector cells in the challenged mice. In addition, DC subsets isolated from mice exposed to nicotine produced significantly less cytokines in response to Th1 adjuvants and inadequately supported the development of Ag-specific Th1 cells. Collectively, our studies suggest that nicotine-induced defects in the DC system compromises vaccine efficacy in smokers.

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The translocation motif of hepatitis B virus improves protein vaccination

Cited by 29 publications

References 30 publications

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

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

Cell-penetrating peptides as a promising tool for delivery of various molecules into the cells

Exposure to Nicotine Adversely Affects the Dendritic Cell System and Compromises Host Response to Vaccination

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