DP7-C-modified liposomes enhance immune responses and the antitumor effect of a neoantigen-based mRNA vaccine

Zhang, Rui; Tang, Lin; Tian, Yaomei; Xiao, Ji; Hu, Qiuyue; Zhou, Bailing; Ding, Zhenyu; Xu, Hong‐Xi; Yang, Li

doi:10.1016/j.jconrel.2020.08.023

Cited by 65 publications

(45 citation statements)

References 38 publications

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“…The addition of DP7-C was found to improve several aspects of antigen presentation in a mouse model such as antigen uptake from monocyte derived DCs, antigen presentation, and presence of mature monocyte-derived DCs [67]. This study also combined the molecule with a liposome for an mRNA vaccine and found significantly higher DC uptake than the control [68], further supporting the use of DP7-C as an immunoadjuvant. Another example is the conjugation of synthetic neoantigen peptides to ligands for tolllike receptors (TLR), acting as agonists to the receptors and further stimulating immune response [69].…”

Section: Immune Primingmentioning

confidence: 52%

Neoantigen Cancer Vaccines: Generation, Optimization, and Therapeutic Targeting Strategies

et al. 2022

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Alternatives to conventional cancer treatments are highly sought after for high-risk malignancies that have a poor response to established treatment modalities. With research advancing rapidly in the past decade, neoantigen-based immunotherapeutic approaches represent an effective and highly tolerable therapeutic option. Neoantigens are tumor-specific antigens that are not expressed in normal cells and possess significant immunogenic potential. Several recent studies have described the conceptual framework and methodologies to generate neoantigen-based vaccines as well as the formulation of appropriate clinical trials to advance this approach for patient care. This review aims to describe some of the key studies in the recent literature in this rapidly evolving field and summarize the current advances in neoantigen identification and selection, vaccine generation and delivery, and the optimization of neoantigen-based therapeutic strategies, including the early data from pivotal clinical studies.

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Section: Immune Primingmentioning

confidence: 52%

Neoantigen Cancer Vaccines: Generation, Optimization, and Therapeutic Targeting Strategies

et al. 2022

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“…3 a-d). In previous studies, we also found that DP7-C treatment increased the proportion of CD103 + DCs (a typology that promotes DC migration) and the efficiency of DC migration to LNs [ 12 , 14 ]. Therefore, we further verified the efficacy of DP7-C in promoting DC migration.…”

Section: Resultsmentioning

confidence: 85%

“…In our previous studies, DP7-C, which is a cholesterol-modified derivative of antimicrobial peptides, was developed and designed by our group using computer simulations and was shown to have both delivery vehicle and immune adjuvant effects, enhancing the antitumor effect of DC vaccines loaded with lung cancer neoantigens [ 12 , 13 ]. In addition, DP7-C-modified liposomes have unique advantages in mRNA delivery and can enhance the antitumor effect of mRNA vaccines encoding lung cancer neoantigens [ 14 ]. Based on the above studies, we intended to conduct clinical trials of DP7-C in combination with a DC vaccine for advanced lung cancer.…”

Section: Introductionmentioning

confidence: 99%

Cholesterol modified DP7 and pantothenic acid induce dendritic cell homing to enhance the efficacy of dendritic cell vaccines

Zhang

Tang

et al. 2021

Mol Biomed

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Dendritic cell (DC)-based cancer vaccines have so far achieved good therapeutic effects in animal experiments and early clinical trials for certain malignant tumors. However, the overall objective response rate in clinical trials rarely exceeds 15%. The poor efficiency of DC migration to lymph nodes (LNs) (< 5%) is one of the main factors limiting the effectiveness of DC vaccines. Therefore, increasing the efficiency of DC migration is expected to further enhance the efficacy of DC vaccines. Here, we used DP7-C (cholesterol modified VQWRIRVAVIRK), which can promote DC migration, as a medium. Through multiomics sequencing and biological experiments, we found that it is the metabolite pantothenic acid (PA) that improves the migration and effectiveness of DC vaccines. We clarified that both DP7-C and PA regulate DC migration by regulating the chemokine receptor CXCR2 and inhibiting miR-142a-3p to affect the NF-κB signaling pathway. This study will lay the foundation for the subsequent use of DP7-C as a universal substance to promote DC migration, further enhance the antitumor effect of DC vaccines, and solve the bottleneck problem of the low migration efficiency and unsatisfactory clinical response rate of DC vaccines.

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“…Another recent example is CB5005, a sequence that contains a Leu-Ala rich hydrophobic domain for cell-penetrating properties and a targeting domain for nuclear localization [79]. The DP7-C sequence is one of such peptides, since it promotes both caveolin-and clathrin-dependent uptake as well as acting as an immune adjuvant, which makes the peptide an excellent ligand for mRNA delivery [80,81]. In fact, most promising peptides for nanocarrier modification are the ones that possess multiple aspects of activity, such as cell-penetrating, targeting, immune adjuvant, antimicrobial or stimuli-responsive properties.…”

Section: Peptides As Targeting Ligands For Lipid Formulationsmentioning

confidence: 99%

Nanocarriers for Biomedicine: From Lipid Formulations to Inorganic and Hybrid Nanoparticles

Kashapov

Ibragimova

Pavlov

et al. 2021

IJMS

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Encapsulation of cargoes in nanocontainers is widely used in different fields to solve the problems of their solubility, homogeneity, stability, protection from unwanted chemical and biological destructive effects, and functional activity improvement. This approach is of special importance in biomedicine, since this makes it possible to reduce the limitations of drug delivery related to the toxicity and side effects of therapeutics, their low bioavailability and biocompatibility. This review highlights current progress in the use of lipid systems to deliver active substances to the human body. Various lipid compositions modified with amphiphilic open-chain and macrocyclic compounds, peptide molecules and alternative target ligands are discussed. Liposome modification also evolves by creating new hybrid structures consisting of organic and inorganic parts. Such nanohybrid platforms include cerasomes, which are considered as alternative nanocarriers allowing to reduce inherent limitations of lipid nanoparticles. Compositions based on mesoporous silica are beginning to acquire no less relevance due to their unique features, such as advanced porous properties, well-proven drug delivery efficiency and their versatility for creating highly efficient nanomaterials. The types of silica nanoparticles, their efficacy in biomedical applications and hybrid inorganic-polymer platforms are the subject of discussion in this review, with current challenges emphasized.

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DP7-C-modified liposomes enhance immune responses and the antitumor effect of a neoantigen-based mRNA vaccine

Cited by 65 publications

References 38 publications

Neoantigen Cancer Vaccines: Generation, Optimization, and Therapeutic Targeting Strategies

Neoantigen Cancer Vaccines: Generation, Optimization, and Therapeutic Targeting Strategies

Cholesterol modified DP7 and pantothenic acid induce dendritic cell homing to enhance the efficacy of dendritic cell vaccines

Nanocarriers for Biomedicine: From Lipid Formulations to Inorganic and Hybrid Nanoparticles

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