mRNA vaccine for cancer immunotherapy

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Feb. 25, 2021

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

Language: Английский

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Tools for translation: non-viral materials for therapeutic mRNA delivery

Nature Reviews Materials, Journal Year: 2017, Volume and Issue: 2(10)

Published: Sept. 12, 2017

Language: Английский

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Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines

Molecular Therapy — Nucleic Acids, Journal Year: 2019, Volume and Issue: 15, P. 1 - 11

Published: Feb. 10, 2019

mRNA vaccines have the potential to tackle many unmet medical needs that are unable be addressed with conventional vaccine technologies. A potent and well-tolerated delivery technology is integral fully realizing of vaccines. Pre-clinical clinical studies demonstrated delivered intramuscularly (IM) first-generation lipid nanoparticles (LNPs) generates robust immune responses. Despite progress made over past several years, there remains significant opportunity for improvement, as most advanced LNPs were designed intravenous (IV) siRNA liver. Here, we screened a panel proprietary biodegradable ionizable lipids both expression immunogenicity in rodent model when administered IM. subset compounds was selected further evaluated tolerability, immunogenicity, rodents non-human primates (NHPs). lead formulation identified yielded response improved tolerability. More importantly vaccines, increased innate stimulation driven by does not equate illustrating tolerability can without affecting potency.

Language: Английский

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Advances in mRNA Vaccines for Infectious Diseases

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: March 27, 2019

During the last two decades, there has been broad interest in RNA-based technologies for development of prophylactic and therapeutic vaccines. Preclinical clinical trials have shown that mRNA vaccines provide a safe long-lasting immune response animal models humans. In this review, we summarize current research progress on vaccines, which potential to be quick-manufactured become powerful tools against infectious disease highlight bright future their design applications.

Language: Английский

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Advances in the delivery of RNA therapeutics: from concept to clinical reality

Genome Medicine, Journal Year: 2017, Volume and Issue: 9(1)

Published: June 27, 2017

The rapid expansion of the available genomic data continues to greatly impact biomedical science and medicine. Fulfilling clinical potential genetic discoveries requires development therapeutics that can specifically modulate expression disease-relevant genes. RNA-based drugs, including short interfering RNAs antisense oligonucleotides, are particularly promising examples this newer class biologics. For over two decades, researchers have been trying overcome major challenges for utilizing such in a therapeutic context, intracellular delivery, stability, immune response activation. This research is finally beginning bear fruit as first RNA drugs gain FDA approval more advance final phases trials. Furthermore, recent advent CRISPR, an RNA-guided gene-editing technology, well new strides delivery messenger transcribed vitro, triggered RNA-therapeutics field. In review, we discuss translation therapeutics, with emphasis on advances technologies, present overview applications modulation gene/protein genome editing currently being investigated both laboratory clinic.

Language: Английский

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Delivery of mRNA vaccines with heterocyclic lipids increases anti-tumor efficacy by STING-mediated immune cell activation

Nature Biotechnology, Journal Year: 2019, Volume and Issue: 37(10), P. 1174 - 1185

Published: Sept. 30, 2019

Language: Английский

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Fenton-Reaction-Acceleratable Magnetic Nanoparticles for Ferroptosis Therapy of Orthotopic Brain Tumors

ACS Nano, Journal Year: 2018, Volume and Issue: 12(11), P. 11355 - 11365

Published: Oct. 30, 2018

Cancer is one of the leading causes morbidity and mortality in world, but more cancer therapies are needed to complement existing regimens due problems therapies. Herein, we term ferroptosis therapy (FT) as a form hypothesize that FT efficacy can be significantly improved via accelerating Fenton reaction by simultaneously increasing local concentrations all reactants (Fe2+, Fe3+, H2O2) cells. Thus, Fenton-reaction-acceleratable magnetic nanoparticles, i.e., cisplatin (CDDP)-loaded Fe3O4/Gd2O3 hybrid nanoparticles with conjugation lactoferrin (LF) RGD dimer (RGD2) (FeGd-HN@Pt@LF/RGD2), were exploited this study for orthotopic brain tumors. FeGd-HN@Pt@LF/RGD2 able cross blood–brain barrier because its small size (6.6 nm) LF-receptor-mediated transcytosis. internalized into cells integrin αvβ3-mediated endocytosis then release Fe2+, CDDP upon endosomal uptake degradation. Fe2+ Fe3+ directly participate reaction, whereas indirectly produce H2O2 further accelerate reaction. The acceleration generates reactive oxygen species induce cell death. successfully delivered involved tumor site led significant inhibition growth. Finally, intrinsic resonance imaging (MRI) capability was used assess monitor response (self-MRI monitoring).

Language: Английский

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Nanomaterial Delivery Systems for mRNA Vaccines

Vaccines, Journal Year: 2021, Volume and Issue: 9(1), P. 65 - 65

Published: Jan. 19, 2021

The recent success of mRNA vaccines in SARS-CoV-2 clinical trials is part due to the development lipid nanoparticle delivery systems that not only efficiently express mRNA-encoded immunogen after intramuscular injection, but also play roles as adjuvants and vaccine reactogenicity. We present an overview then focus on nanoparticles used current trials. review concludes with analysis determinants performance vaccines.

Language: Английский

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Ionizable Lipid Nanoparticle-Mediated mRNA Delivery for Human CAR T Cell Engineering

Nano Letters, Journal Year: 2020, Volume and Issue: 20(3), P. 1578 - 1589

Published: Jan. 17, 2020

Chimeric antigen receptor (CAR) T cell therapy relies on the ex vivo manipulation of patient cells to create potent, cancer-targeting therapies, shown be capable inducing remission in patients with acute lymphoblastic leukemia and large B lymphoma. However, current CAR engineering methods use viral delivery vectors, which induce permanent expression could lead severe adverse effects. Messenger RNA (mRNA) has been explored as a promising strategy for transient mitigate effects associated but it most commonly requires electroporation mRNA delivery, can cytotoxic. Here, ionizable lipid nanoparticles (LNPs) were designed human cells. A library 24 lipids was synthesized, formulated into LNPs, screened luciferase Jurkat cells, revealing seven formulations enhanced over lipofectamine. The top-performing LNP formulation, C14–4, selected primary This platform induced at levels equivalent electroporation, substantially reduced cytotoxicity. engineered via C14–4 treatment then compared electroporated coculture assay Nalm-6 both elicited potent cancer-killing activity. These results demonstrate ability LNPs deliver functional protein expression, indicate potential enhance mRNA-based methods.

Language: Английский

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Lipid nanoparticles for nucleic acid delivery: Current perspectives

Advanced Drug Delivery Reviews, Journal Year: 2020, Volume and Issue: 154-155, P. 37 - 63

Published: Jan. 1, 2020

Language: Английский

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