Engineering Lipid Nanoparticles for mRNA Immunotherapy DOI Creative Commons
Robby Zwolsman, Y. Darwish, Ewelina Kluza

et al.

Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology, Journal Year: 2025, Volume and Issue: 17(2)

Published: March 1, 2025

ABSTRACT Over the last decades, messenger RNA (mRNA) has emerged as a promising therapeutic modality, enabling delivery of genetic instructions to cells for producing proteins or antigens. As such, mRNA‐based therapies can be developed wide range conditions, including infections, cancer, metabolic disorders, and diseases. Nevertheless, using mRNA therapeutically requires chemical modifications reduce immunostimulatory effects nanotechnology prevent degradation ensure intracellular delivery. Lipid nanoparticles (LNPs) have become most effective platform therapeutics, which are primarily employed vaccine purposes following local administration hepatic applications systemic administration. Here, we review state‐of‐the‐art LNP‐mRNA technology discuss its potential immunotherapy. We first outline requirements used therapeutically, role LNP‐mediated Next, highlight immunotherapy approaches vaccination, immuno‐oncology, autoimmune disorders. In addition, challenges that limiting LNP‐mRNA's widespread use, tunable biodistribution effects. Finally, provide an outlook on how implementing such library screening machine learning will guide development next‐generation therapeutics.

Language: Английский

Lipid Nanoparticle (LNP) Delivery Carrier-Assisted Targeted Controlled Release mRNA Vaccines in Tumor Immunity DOI Creative Commons
Liusheng Wu, Xiaoqiang Li,

Xinye Qian

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 12(2), P. 186 - 186

Published: Feb. 12, 2024

In recent years, lipid nanoparticles (LNPs) have attracted extensive attention in tumor immunotherapy. Targeting immune cells cancer therapy has become a strategy of great research interest. mRNA vaccines are potential choice for immunotherapy, due to their ability directly encode antigen proteins and stimulate strong response. However, the mode delivery lack stability key issues limiting its application. LNPs an excellent carrier, structural biocompatibility make them effective means delivering specific targets. This study summarizes progress LNP carrier-assisted targeted controlled release immunity. The role improving stability, immunogenicity, targeting is discussed. review aims systematically summarize latest immunity provide new ideas strategies as well more treatment plans patients.

Language: Английский

Citations

53
Direct in vivo CAR T cell engineering DOI Creative Commons

Lauralie Short,

Robert A. Holt, Pieter R. Cullis

et al.

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(5), P. 406 - 418

Published: April 12, 2024

T cells modified to express intelligently designed chimeric antigen receptors (CARs) are exceptionally powerful therapeutic agents for relapsed and refractory blood cancers have the potential revolutionize therapy many other diseases. To circumvent complexity cost associated with broad-scale implementation of ex vivo manufactured adoptive cell products, alternative strategies generate CAR in by direct infusion nanoparticle-formulated nucleic acids or engineered viral vectors under development received a great deal attention past few years. Here, we outline manufacturing process as motivating framework discuss emerging data from preclinical models highlight potency approach, applicability new disease indications, remaining challenges clinical readiness, including delivery specificity, long term efficacy, safety.

Language: Английский

Citations

22
A new era of cancer immunotherapy: combining revolutionary technologies for enhanced CAR-M therapy DOI Creative Commons
Na Li,

Shinan Geng,

Zhenzhen Dong

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: June 1, 2024

Abstract Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during previous ten years. However, its effectiveness treating solid tumors is still lacking, necessitating exploration alternative immunotherapies that can overcome significant challenges faced by current CAR-T cells. CAR-based immunotherapy against shows promise with emergence macrophages, which possess robust phagocytic abilities, antigen-presenting functions, and ability to modify tumor microenvironment stimulate adaptive responses. This paper presents a thorough examination latest progress CAR-M therapy, covering both basic scientific studies clinical trials. study examines primary obstacles hindering realization complete potential as well strategies be employed these hurdles. With revolutionary technologies like situ genetic modification, synthetic biology techniques, biomaterial-supported gene transfer, provide wider array resources manipulating tumor-associated we suggest combining advanced methods will result creation new era therapy demonstrates improved efficacy, safety, availability. Graphical

Language: Английский

Citations

20
Prospects and challenges of CAR-T cell therapy combined with ICIs DOI Creative Commons

Yufan Lv,

Xinyu Luo,

Zhuoyi Xie

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: March 20, 2024

Immune checkpoint molecules are a group of expressed on the surface immune cells that primarily regulate their homeostasis. Chimeric antigen receptor (CAR) T cell therapy is an immunotherapeutic technology realizes tumor-targeted killing by constructing synthetic expressing specific antigens through biotechnology. Currently, CAR-T has achieved good efficacy in non-solid tumors, but its treatment solid tumors not yielded desired results. inhibitors (ICIs) combined with novel combination high expectations to defeat tumors. This review addresses challenges and this

Language: Английский

Citations

17
Rational formulation and industrial manufacturing of lipid-based complex injectables: Landmarks and trends DOI

Mariana Biscaia-Caleiras,

Nuno A. Fonseca, Ana Sofia Lourenço

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 373, P. 617 - 639

Published: July 31, 2024

Language: Английский

Citations

15
Lipid nanoparticle (LNP) mediated mRNA delivery in cardiovascular diseases: Advances in genome editing and CAR T cell therapy DOI

Setareh Soroudi,

Mahmoud Reza Jaafari,

Leila Arabi

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 372, P. 113 - 140

Published: June 15, 2024

Language: Английский

Citations

10
Kinetics of RNA-LNP delivery and protein expression DOI Creative Commons
Judith Müller, Nathalie Gabriele Schäffler, Thomas Kellerer

et al.

European Journal of Pharmaceutics and Biopharmaceutics, Journal Year: 2024, Volume and Issue: 197, P. 114222 - 114222

Published: Feb. 20, 2024

Lipid nanoparticles (LNPs) employing ionizable lipids are the most advanced technology for delivery of RNA, notably mRNA, to cells. LNPs represent well-defined core–shell particles with efficient nucleic acid encapsulation, low immunogenicity and enhanced efficacy. While much is known about structure activity LNPs, less attention given timing LNP uptake, cytosolic transfer protein expression. However, kinetics a key factor determining efficiency. Hence quantitative insight into multi-cascaded pathway interest elucidate mechanism delivery. Here, we review experiments as well theoretical modeling mRNA-release We describe sequence stochastic processes mathematical model subsequent translation from mRNA. compile probabilities numbers obtained time resolved microscopy. Specifically, live-cell imaging on single cell arrays (LISCA) allows high-throughput acquisition thousands individual GFP reporter expression courses. The traces yield distribution mRNA life-times, rates onset. Correlation analysis reveals an inverse dependence gene efficiency transfection onset-times. Finally, discuss why release critical in context codelivery multiple species case co-expression or CRISPR/Cas editing.

Language: Английский

Citations

9
Emerging strategies for nanomedicine in autoimmunity DOI
Ajay S. Thatte, Margaret M. Billingsley, Drew Weissman

et al.

Advanced Drug Delivery Reviews, Journal Year: 2024, Volume and Issue: 207, P. 115194 - 115194

Published: Feb. 10, 2024

Language: Английский

Citations

9
Investigating the delivery of PD-L1-targeted immunoliposomes in a dynamic cervical cancer-on-a-chip model DOI Creative Commons
Seth‐Frerich Fobian, Mohamadreza Amin, Andrea Sacchetti

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 379, P. 236 - 250

Published: Jan. 11, 2025

The recent approval of pembrolizumab in recurrent or metastatic cervical cancer warrants further investigations into the usefulness immunotherapies for more durable and less radical interventions. In this study, targeting potential anti-PD-L1-functionalized immunoliposomes was tested a 3D vitro cancer-on-a-chip model. Immunolipsomes were synthesized decorated externally with monovalent anti-PD-L1 Fab' fragments commercially available atezolizumab. Cervical cell lines varying levels PD-L1 expression cultured as spheroids embedded collagen I matrix, treated under flow culture media. Flow cytometry live-cell confocal imaging used to measure interactions uptake untargeted liposomes panel lines. retained specific functionality regardless protein corona formation high serum environments. As such, expressing preferentially internalized environment extracellular matrix present, while low PD-L1-expressing showed no preference either formulation. Importantly, treatments performed monolayer cultures (on plastic) differences between immuno- liposome uptake, including way which endocytosed are trafficked subcellularly. This study demonstrates importance both active passive accumulation strategies achieve nanoparticle targeting. Immunoliposomes remain promising platform development targeted nanotherapies against cancers. However, initial functional tests did not translate directly biological performance should be kept mind future formulations. Furthermore, model developed appeared useful visualizing 3D, live tissue represents cost-effective reproducible studies.

Language: Английский

Citations

1
High-Throughput In Vivo Screening Identifies Differential Influences on mRNA Lipid Nanoparticle Immune Cell Delivery by Administration Route DOI
Alex G. Hamilton, Kelsey L. Swingle, Ajay S. Thatte

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(25), P. 16151 - 16165

Published: June 11, 2024

Immune modulation through the intracellular delivery of nucleoside-modified mRNA to immune cells is an attractive approach for in vivo immunoengineering, with applications infectious disease, cancer immunotherapy, and beyond. Lipid nanoparticles (LNPs) have come fore as a promising nucleic acid platform, but LNP design criteria remain poorly defined, making rate-limiting step discovery screening process. In this study, we employed high-throughput based on molecular barcoding investigate influence composition tropism vaccines systemic immunotherapies. Screening large library under both intramuscular (i.m.) intravenous (i.v.) injection, observed differential influences uptake by populations across two administration routes, gleaning insight into immunoengineering. validation studies, lead formulation i.m. demonstrated substantial translation spleen draining lymph nodes more favorable biodistribution profile than LNPs formulated clinical standard ionizable lipid DLin-MC3-DMA (MC3). The formulations i.v. displayed potent transfection peripheral blood, one demonstrating splenic dendritic another inducing circulating monocytes. Altogether, immunotropic identified significant promise locally- systemically-delivered confirmed value gleaned from our process, which could potentially inform future endeavors vaccine immunotherapy applications.

Language: Английский

Citations

8