Adjuvant-pulsed mRNA vaccine nanoparticle for immunoprophylactic and therapeutic tumor suppression in mice

Islam, Mohammad Ariful; Rice, Jamie; Reesor, Emma; Zope, Harshal; Tao, Wei; Lim, Michael; Ding, Jianxun; Chen, Yunhan; Aduluso, Dike; Zetter, Bruce R.; Farokhzad, Omid C.; Shi, Jinjun

doi:10.1016/j.biomaterials.2020.120431

Cited by 154 publications

(135 citation statements)

References 78 publications

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“…Recently, Islam et al demonstrated that mRNA vaccine pulsed with R848 adjuvant exhibits the anti-tumor efficacy in syngeneic mouse models of prostate cancer. 47 Our data prove that PLGA-ICG-R848 induced the significant maturation of BMDCs, and its combination with laser ablation increased the proportion of splenic NK cells, which may further contribute to a stronger anticancer efficacy against PCa. Further studies to evaluate the anti-metastasis effect and long-term maintenance of immunological memory against PCa are also required to better understand the therapeutic potential of PLGA-ICG-R848 NPs with NIR laser.…”

Section: Discussionsupporting

confidence: 63%

Dual-Functional PLGA Nanoparticles Co-Loaded with Indocyanine Green and Resiquimod for Prostate Cancer Treatment

Lin¹,

Li²,

Xu³

et al. 2021

IJN

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Purpose With the advance of screening techniques, there is a growing number of low-risk or intermediate-risk prostate cancer (PCa) cases, remaining a serious threat to men’s health. To obtain better efficacy, a growing interest has been attracted to develop such emerging treatments as immunotherapy and focal therapy. However, few studies offer guidance on whether and how to combine these modalities against PCa. This study was designed to develop dual-functional nanoparticles (NPs) which combined photothermal therapy (PTT) with immunotherapy and determine the anti-tumor efficacy for PCa treatment. Methods By a double emulsion technique, the drug nanocarrier, poly(lactic-co-glycolic acid) or PLGA, was applied for co-loading of a fluorescent dye, indocyanine green (ICG) and a toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) to synthesize PLGA-ICG-R848 NPs. Next, we determined their characteristic features and evaluated whether they inhibited the cell viability in multiple PCa cell lines. After treatment with PLGA-ICG-R848, the maturation markers of bone marrow-derived dendritic cells (BMDCs) were detected by flow cytometry. By establishing a subcutaneous xenograft model of mouse PCa, we explored both the anti-tumor effect and immune response following the NPs-based laser ablation. Results With a mean diameter of 157.7 nm, PLGA-ICG-R848 exhibited no cytotoxic effect in PCa cells, but they significantly decreased RM9 cell viability to (3.9±1.0)% after laser irradiation. Moreover, PLGA-ICG-R848 promoted BMDCs maturation with the significantly elevated proportions of CD11c+CD86+ and CD11c+CD80+ cells. Following PLGA-ICG-R848-based laser ablation in vivo, the decreased bioluminescent signals indicated a significant inhibition of PCa growth, while the ratio of splenic natural killer (NK) cells in PLGA-ICG-R848 was (3.96±1.88)% compared with (0.99±0.10)% in PBS group, revealing the enhanced immune response against PCa. Conclusion The dual-functional PLGA-ICG-R848 NPs under laser irradiation exhibit the anti-tumor efficacy for PCa treatment by combining PTT with immunotherapy.

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Section: Discussionsupporting

confidence: 63%

Dual-Functional PLGA Nanoparticles Co-Loaded with Indocyanine Green and Resiquimod for Prostate Cancer Treatment

Lin¹,

Li²,

Xu³

et al. 2021

IJN

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“…Other studies indicated that enhanced immune responses via combination with alternative adjuvants are required for mRNA vaccines to achieve the targeted anti-tumor therapeutic outcome and improved patients’ survival. Islam and coworkers have reported mRNA pulsed with a palmitic acid-modified TLR7/8 agonist R484 markedly improved the MHC class I presentation of OVA mRNA derived antigen in APCs, subsequently induced a more effective adaptive immune response in a tumor bearing mouse model as compared to mRNA vaccine without the adjuvant [ 55 ]. Moreover, the RNActive® vaccine platform developed by CureVac AG.…”

Section: Strategies To Improve Mrna Translation Efficiency and Overcomentioning

confidence: 99%

“…Islam and coworkers utilized a modified PAMAM dendrimers, PLGA and ceramide PEG to formulate polymer-lipid hybrid nanoparticles to deliver phosphate and tensin homolog mRNA in vivo [ 114 ]. In a later study, they utilized the same vehicle to deliver OVA mRNA vaccine together with a fatty acid modified TLR7/8 agonist C16-R848, and showed the combination formulation could boost a strong antitumor immunogenicity [ 55 ].…”

Section: Delivery Of Mrna Cancer Vaccinementioning

confidence: 99%

“…Representative examples include: i.m. injection of PAMAM loaded OVA mRNA for melanoma treatment in mice [ 55 ], Moderna LNPs optimized for i.m injection of mRNA vaccines [ 54 ], s.c. injection of peptide modified DOTAP liposomes, s.c. injection of LNPs with optimized lipid compositions and lipid structures for antitumor vaccinations [ 26 ], i.d. injection of LPR to boost anti-cancer immunity in multiple mouse models [ 131 ].…”

Section: Delivery Of Mrna Cancer Vaccinementioning

confidence: 99%

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mRNA vaccine for cancer immunotherapy

2021

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AbstractmRNA vaccines have become a promising platform for cancer immunotherapy. During vaccination, naked or vehicle loaded mRNA vaccines efficiently express tumor antigens in antigen-presenting cells (APCs), facilitate APC activation and innate/adaptive immune stimulation. mRNA cancer vaccine precedes other conventional vaccine platforms due to high potency, safe administration, rapid development potentials, and cost-effective manufacturing. However, mRNA vaccine applications have been limited by instability, innate immunogenicity, and inefficient in vivo delivery. Appropriate mRNA structure modifications (i.e., codon optimizations, nucleotide modifications, self-amplifying mRNAs, etc.) and formulation methods (i.e., lipid nanoparticles (LNPs), polymers, peptides, etc.) have been investigated to overcome these issues. Tuning the administration routes and co-delivery of multiple mRNA vaccines with other immunotherapeutic agents (e.g., checkpoint inhibitors) have further boosted the host anti-tumor immunity and increased the likelihood of tumor cell eradication. With the recent U.S. Food and Drug Administration (FDA) approvals of LNP-loaded mRNA vaccines for the prevention of COVID-19 and the promising therapeutic outcomes of mRNA cancer vaccines achieved in several clinical trials against multiple aggressive solid tumors, we envision the rapid advancing of mRNA vaccines for cancer immunotherapy in the near future. This review provides a detailed overview of the recent progress and existing challenges of mRNA cancer vaccines and future considerations of applying mRNA vaccine for cancer immunotherapies.

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“…mRNA encoding the tumor antigen TRP2, transfected using a formulation which contained the TLR–agonist LPS, resulted in prolonged survival in a B16F10 melanoma model 123 . Similar strategies, combining mRNA to other TLR agonists, like the small molecule R848, have also been proposed 124 .…”

Section: The Adaptive Immunitymentioning

confidence: 99%

Innate and adaptive immune responses toward nanomedicines

Viana

Roussel

Defrêne

et al. 2021

Acta Pharmaceutica Sinica B

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Since the commercialization of the first liposomes used for drug delivery, Doxil/Caelyx® and Myocet, tremendous progress has been made in understanding interactions between nanomedicines and biological systems. Fundamental work at the interface of engineering and medicine has allowed nanomedicines to deliver therapeutic small molecules and nucleic acids more efficiently. While nanomedicines are used in oncology for immunotherapy or to deliver combinations of cytotoxics, the clinical successes of gene silencing approaches like patisiran lipid complexes (Onpattro®) have paved the way for a variety of therapies beyond cancer. In parallel, the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted the potential of mRNA vaccines to develop immunization strategies at unprecedented speed. To rationally design therapeutic and vaccines, chemists, materials scientists, and drug delivery experts need to better understand how nanotechnologies interact with the immune system. This review presents a comprehensive overview of the innate and adaptative immune systems and emphasizes the intricate mechanisms through which nanomedicines interact with these biological functions.

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Adjuvant-pulsed mRNA vaccine nanoparticle for immunoprophylactic and therapeutic tumor suppression in mice

Cited by 154 publications

References 78 publications

Dual-Functional PLGA Nanoparticles Co-Loaded with Indocyanine Green and Resiquimod for Prostate Cancer Treatment

Dual-Functional PLGA Nanoparticles Co-Loaded with Indocyanine Green and Resiquimod for Prostate Cancer Treatment

mRNA vaccine for cancer immunotherapy

Innate and adaptive immune responses toward nanomedicines

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