Lipid nanoparticles of Type-A CpG D35 suppress tumor growth by changing tumor immune-microenvironment and activate CD8 T cells in mice

Munakata, Lisa; Tanimoto, Yuko; Osa, Akio; Meng, Jie; Haseda, Yasunari; Naito, Yujiro; Machiyama, Hirotomo; Kumanogoh, Atsushi; Omata, Daiki; Maruyama, Kazuo; Yoshioka, Yasuo; Okada, Yoshiaki; Koyama, Shohei; Suzuki, Ryo; Aoshi, Taiki

doi:10.1016/j.jconrel.2019.09.011

Cited by 40 publications

(36 citation statements)

References 55 publications

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“…The hydrodynamic diameter of the LNP was 86.5 nm (polydispersity index: 0.277), and the zeta potential of the LNP was 67.9 ± 12.1 mV. We had already confirmed the physical properties of LNP-CpG: The hydrodynamic diameter of LNP-CpG was 54.0 nm (polydispersity index: 0.157), and the zeta potential of LNP-CpG was 1.12 ± 8.26 mV [ 26 , 27 ].…”

Section: Resultsmentioning

confidence: 94%

“…We investigated the usefulness of the LNP as an adjuvant and compared the immune responses induced by the LNP, LNP-CpG, and alum. The LNP and LNP-CpG were prepared by using a microfluidic mixer system, NanoAssemblr, as described previously [ 26 , 27 ]. The hydrodynamic diameter of the LNP was 86.5 nm (polydispersity index: 0.277), and the zeta potential of the LNP was 67.9 ± 12.1 mV.…”

Section: Resultsmentioning

confidence: 99%

“…The prepared LNP was filtered through a 0.22-μm PVDF filter (Merck KGaA, Darmstadt, Germany). An LNP containing CpG ODN (LNP-CpG) was also prepared by using NanoAssemblr Benchtop, as described previously [ 26 , 27 ]. All LNP preparation work was performed at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…We have demonstrated the potential of the LNP we developed as a CpG ODN delivery vehicle [ 26 , 27 ]. We have already demonstrated that LNP containing CpG ODN (LNP-CpG) has stronger immune-activating activity in vitro and in vivo than CpG ODN [ 26 , 27 ]. In addition, LNP-CpG induces stronger antigen-specific antibody responses than CpG ODN in mice vaccinated with SV generated from influenza virus [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Lipid Nanoparticle Acts as a Potential Adjuvant for Influenza Split Vaccine without Inducing Inflammatory Responses

et al. 2020

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Vaccination is a critical and reliable strategy for controlling the spread of influenza viruses in populations. Conventional seasonal split vaccines (SVs) for influenza evoke weaker immune responses than other types of vaccines, such as inactivated whole-virion vaccines, although SVs are highly safe compared to other types. Here, we assessed the potential of the lipid nanoparticle (LNP) we developed as an adjuvant for conventional influenza SV as an antigen in mice. The LNP did not induce the production of cytokines such as interleukin-6 (IL-6) and IL-12 p40 by dendritic cells or the expression of co-stimulatory molecules on these cells in vitro. In contrast, an SV adjuvanted with LNP improved SV-specific IgG1 and IgG2 responses and the Th1 response compared to the SV alone in mice. In addition, SV adjuvanted with an LNP gave superior protection against the influenza virus challenge over the SV alone and was as effective as SV adjuvanted with aluminum salts in mice. The LNP did not provoke inflammatory responses such as inflammatory cytokine production and inflammatory immune cell infiltration in mice, whereas aluminum salts induced inflammatory responses. These results suggest the potential of the LNP as an adjuvant without inflammatory responses for influenza SVs. Our strategy should be useful for developing influenza vaccines with enhanced efficacy and safety.

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Lipid Nanoparticle Acts as a Potential Adjuvant for Influenza Split Vaccine without Inducing Inflammatory Responses

et al. 2020

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“…An expression and purification system of the soluble tetramer was established. Purified protein was administered to mice with adjuvants including the widely used aluminum hydroxide gel adjuvant (Alum) and D35, which belongs to the group of CpG oligodeoxynucleotide adjuvants, which showed advantages in inducing cellular immunity by stimulating the innate immune receptor, toll-like receptor 9 (TLR9) [28,29]. Our analyses of both humoral and cellular immunity corroborated the effectiveness of the use of the tetramer as a prophylactic subunit vaccine.…”

Section: Introductionmentioning

confidence: 52%

Tetrameric glycoprotein complex gH/gL/gQ1/gQ2 is a promising vaccine candidate for human herpesvirus 6B

et al. 2020

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Primary infection of human herpesvirus 6B (HHV-6B) occurs in infants after the decline of maternal immunity and causes exanthema subitum accompanied by a high fever, and it occasionally develops into encephalitis resulting in neurological sequelae. There is no effective prophylaxis for HHV-6B, and its development is urgently needed. The glycoprotein complex gH/gL/gQ1/gQ2 (called 'tetramer of HHV-6B') on the virion surface is a viral ligand for its cellular receptor human CD134, and their interaction is thus essential for virus entry into the cells. Herein we examined the potency of the tetramer as a vaccine candidate against HHV-6B. We designed a soluble form of the tetramer by replacing the transmembrane domain of gH with a cleavable tag, and the tetramer was expressed by a mammalian cell expression system. The expressed recombinant tetramer is capable of binding to hCD134. The tetramer was purified to homogeneity and then administered to mice with aluminum hydrogel adjuvant and/or CpG oligodeoxynucleotide adjuvant. After several immunizations, humoral and cellular immunity for HHV-6B was induced in the mice. These results suggest that the tetramer together with an adjuvant could be a promising candidate HHV-6B vaccine.

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A pH‐Responsive Cluster Metal–Organic Framework Nanoparticle for Enhanced Tumor Accumulation and Antitumor Effect

et al. 2022

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As a result of the deficient tumor‐specific antigens, potential off‐target effect, and influence of protein corona, metal–organic framework nanoparticles have inadequate accumulation in tumor tissues, limiting their therapeutic effects. In this work, a pH‐responsive linker (L) is prepared by covalently modifying oleylamine (OA) with 3‐(bromomethyl)‐4‐methyl‐2,5‐furandione (MMfu) and poly(ethylene glycol) (PEG). Then, the L is embedded into a solid lipid nanoshell to coat apilimod (Ap)‐loaded zeolitic imidazolate framework (Ap‐ZIF) to form Ap‐ZIF@SLN#L. Under the tumor microenvironment, the hydrophilic PEG and MMfu are removed, exposing the hydrophobic OA on Ap‐ZIF@SLN#L, increasing their uptake in cancer cells and accumulation in the tumor. The ZIF@SLN#L nanoparticle induces reactive oxygen species (ROS). Ap released from Ap‐ZIF@SLN#L significantly promotes intracellular ROS and lactate dehydrogenase generation. Ap‐ZIF@SLN#L inhibits tumor growth, increases the survival rate in mice, activates the tumor microenvironment, and improves the infiltration of macrophages and T cells in the tumor, as demonstrated in two different tumor‐bearing mice after injections with Ap‐ZIF@SLN#TL. Furthermore, mice show normal tissue structure of the main organs and the normal serum level in alanine aminotransferase and aspartate aminotransferase after treatment with the nanoparticles. Overall, this pH‐responsive targeting strategy improves nanoparticle accumulation in tumors with enhanced therapeutic effects.

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Lipid nanoparticles of Type-A CpG D35 suppress tumor growth by changing tumor immune-microenvironment and activate CD8 T cells in mice

Cited by 40 publications

References 55 publications

Lipid Nanoparticle Acts as a Potential Adjuvant for Influenza Split Vaccine without Inducing Inflammatory Responses

Lipid Nanoparticle Acts as a Potential Adjuvant for Influenza Split Vaccine without Inducing Inflammatory Responses

Tetrameric glycoprotein complex gH/gL/gQ1/gQ2 is a promising vaccine candidate for human herpesvirus 6B

A pH‐Responsive Cluster Metal–Organic Framework Nanoparticle for Enhanced Tumor Accumulation and Antitumor Effect

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