Efficient co-delivery of neo-epitopes using dispersion-stable layered double hydroxide nanoparticles for enhanced melanoma immunotherapy

Zhang, Lingxiao; Xie, Xin; Liu, Dong‐qun; Xu, Zhi Ping

doi:10.1016/j.biomaterials.2018.05.015

Cited by 94 publications

(82 citation statements)

References 57 publications

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“…However, the development of tumor is always accompanied by mutations in a variety of proteins, which limits the outcome of a vaccine targeting just one mutant protein for tumor inhibition and elimination. To enhance the antitumor immunity, two mutated epitope peptides (the immunogenic determinant of an antigen) and a model antigen were coloaded into layered double hydroxide nanoparticles to induce very strong CTL responses . Compared with counterparts with single antigen, personalized multiantigen nanovaccine may act as a potent platform against immune tolerance and achieve remarkable inhibition of melanoma growth.…”

Section: Nanomaterials For Traditional and Novel Vaccine Deliverymentioning

confidence: 99%

Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

Liu

Zhang

2019

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Cancer immunotherapy is a promising cancer terminator by directing the patient's own immune system in the fight against this challenging disorder. Despite the monumental therapeutic potential of several immunotherapy strategies in clinical applications, the efficacious responses of a wide range of immunotherapeutic agents are limited in virtue of their inadequate accumulation in the tumor tissue and fatal side effects. In the last decades, increasing evidences disclose that nanotechnology acts as an appealing solution to address these technical barriers via conferring rational physicochemical properties to nanomaterials. In this Review, an imperative emphasis will be drawn from the current understanding of the effect of a nanosystem's structure characteristics (e.g., size, shape, surface charge, elasticity) and its chemical modification on its transport and biodistribution behavior. Subsequently, rapid‐moving advances of nanoparticle‐based cancer immunotherapies are summarized from traditional vaccine strategies to recent novel approaches, including delivery of immunotherapeutics (such as whole cancer cell vaccines, immune checkpoint blockade, and immunogenic cell death) and engineered immune cells, to regulate tumor microenvironment and activate cellular immunity. The future prospects may involve in the rational combination of a few immunotherapies for more efficient cancer inhibition and elimination.

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Section: Nanomaterials For Traditional and Novel Vaccine Deliverymentioning

confidence: 99%

Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

Liu

Zhang

2019

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116

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“…The current study also demonstrated that sustained antigen release can be accomplished using an LDH nano-adjuvant, which promotes antigen presentation and produces a long-lasting and efficient memory immune response, thus reducing the number of vaccinations and the amount of antigen [31][32][33][34]. In this study, antibody levels in mice immunized with LDH + FMDV were significantly higher from day 42 to day 98 compared to the saline group (P < 0.01) and were significantly higher compared with the ISA-206 group on day 56 (P < 0.05).…”

Section: Discussionmentioning

confidence: 64%

“…LDH-adjuvanted multiple-antigen vaccine formulations can efficiently stimulate strong humoral, cellular and mucosal immune responses that are capable of preventing E. coli from adhering to mammalian cells more efficiently than the commercial adjuvant formulation [27,33]. A dispersionstable LDH-based vaccine induced stronger cytotoxic T-lymphocyte (CTL) responses and significantly inhibited tumor growth [34]. Therefore, LDH is a promising adjuvant vaccine due to the small particle size, stable dispersion, large specific surface area, positive charge, large cargo load, sustained release, easy absorption, low toxicity, low cost, and significantly improved the cellular immune response.…”

Section: Layered Double Hydroxide (Ldh) Is Hydrotalcite-like Clay Rementioning

confidence: 99%

LDHs enhanced the immune response of animals to foot-and-mouth disease virus

Zhang

Yin

et al. 2020

Preprint

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Background: Foot-and-mouth disease (FMD) is a highly transmissible disease that leads to vast economic losses in many countries. Prevention using inactivated vaccines is one effective measure used to control FMD. Unfortunately, inactivated FMD vaccines provide only short-term protection and require a cold-chain system. In recent years, many studies have shown that layered double metal hydroxides (LDHs) carrying antigens can be used to strongly induce immune responses. In this study, LDH nanoparticles (NPs) were prepared by hydrothermal synthesis. LDH particle size, electric potential, and morphology were measured and observed. The adsorption capacity of LDH NPs to FMDV was tested. The effects of LDH as an adjuvant on inactivated FMDV vaccines were further evaluated and compared with commercial FMDV ISA-206 in BALB/C female mice and Yorkshire pigs.Results: LDH NPs were successfully prepared with a uniform particle size of ~87.21 nm, regular edges, a loose hexagonal shape and positive zeta charge of 32 mV. The maximum absorption concentration was 0.16-0.31 µg FMDV/µg LDH. In the mouse experiment, antibody of immunized with LDH + FMDV were induced significantly higher from days 42-98 compared to saline + FMDV (P<0.01) and significantly higher compared to ISA-206+FMDV on day 56 post-immunization (P<0.05). After day14 post-immunization, IFN-γ content was significantly increased (P<0.05). In the pig experiment, antibody levels in both the ISA-206 + FMDV and LDH + FMDV were positive and were significantly higher compared with the PBS group on day 7 (P<0.005). Antibody levels in 90% pigs were positive on day 56 in the LDH group. The neutralizing antibody levels in the LDH and ISA-206 groups were significantly higher from days 7-28 compared to the PBS control group (P<0.05). Thus, LDH NPs were effective at inducing an immune response against FMDV.Conclusions: LDHs with a loose hexagonal shape and a positive charge were prepared. LDHs can effectively induce humoral- and cell-mediated immune responses in mice and pigs. In addition, the LDHs had a slow-release effect and produced antibodies continuously. LDHs may act as an excellent FMDV adjuvant.

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“…Other examples of inorganic nanovaccines include using MgAl‐layered double hydroxide (LDH) nanoparticles to codeliver CpG and peptide antigens; using zinc‐doped iron oxide magnetic nanoparticle‐loaded phospholipid micelles to codeliver poly I:C, TLR3 agonist and OVA peptide antigens; using lipid‐coated zinc phosphate hybrid nanoparticles to codeliver multiple peptide antigens and TLR 4 agonist; using liposome‐coated gold nanoparticles with anti‐CD11c targeting ligands to codeliver MPLA adjuvant and TRP2 peptide antigen; and using multiwalled carbon nanotubes to codeliver CpG, OVA and anti‐CD40 …”

Section: Nanotechnology For Cancer Vaccine Developmentmentioning

confidence: 99%

Emerging Nano‐/Microapproaches for Cancer Immunotherapy

et al. 2019

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Cancer immunotherapy has achieved remarkable clinical efficacy through recent advances such as chimeric antigen receptor‐T cell (CAR‐T) therapy, immune checkpoint blockade (ICB) therapy, and neoantigen vaccines. However, application of immunotherapy in a clinical setting has been limited by low durable response rates and immune‐related adverse events. The rapid development of nano‐/microtechnologies in the past decade provides potential strategies to improve cancer immunotherapy. Advances of nano‐/microparticles such as virus‐like size, high surface to volume ratio, and modifiable surfaces for precise targeting of specific cell types can be exploited in the design of cancer vaccines and delivery of immunomodulators. Here, the emerging nano‐/microapproaches in the field of cancer vaccines, immune checkpoint blockade, and adoptive or indirect immunotherapies are summarized. How nano‐/microparticles improve the efficacy of these therapies, relevant immunological mechanisms, and how nano‐/microparticle methods are able to accelerate the clinical translation of cancer immunotherapy are explored.

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Efficient co-delivery of neo-epitopes using dispersion-stable layered double hydroxide nanoparticles for enhanced melanoma immunotherapy

Cited by 94 publications

References 57 publications

Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

Nanoparticle‐Based Nanomedicines to Promote Cancer Immunotherapy: Recent Advances and Future Directions

LDHs enhanced the immune response of animals to foot-and-mouth disease virus

Emerging Nano‐/Microapproaches for Cancer Immunotherapy

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