Challenges and new technologies in adoptive cell therapy DOI Creative Commons
Pengchao Zhang, Guizhong Zhang, Xiaochun Wan

et al.

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Aug. 18, 2023

Abstract Adoptive cell therapies (ACTs) have existed for decades. From the initial infusion of tumor-infiltrating lymphocytes to subsequent specific enhanced T receptor (TCR)-T and chimeric antigen (CAR)-T therapies, many novel strategies cancer treatment been developed. Owing its promising outcomes, CAR-T therapy has revolutionized field ACTs, particularly hematologic malignancies. Despite these advances, still limitations in both autologous allogeneic settings, including practicality toxicity issues. To overcome challenges, researchers focused on application CAR engineering technology other types immune engineering. Consequently, several new based developed, CAR-NK, CAR-macrophage, CAR-γδT, CAR-NKT. In this review, we describe development, advantages, possible challenges aforementioned ACTs discuss current aimed at maximizing therapeutic potential ACTs. We also provide an overview various gene transduction employed immunotherapy given their importance Furthermore, possibility that capable creating a positive feedback circuit, as healthy systems do, could address flaw single type ACT, thus serve key players future immunotherapy.

Language: Английский

Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins DOI Creative Commons
Samagya Banskota, Aditya Raguram, Susie Suh

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(2), P. 250 - 265.e16

Published: Jan. 1, 2022

Methods to deliver gene editing agents in vivo as ribonucleoproteins could offer safety advantages over nucleic acid delivery approaches. We report the development and application of engineered DNA-free virus-like particles (eVLPs) that efficiently package base editor or Cas9 ribonucleoproteins. By engineering VLPs overcome cargo packaging, release, localization bottlenecks, we developed fourth-generation eVLPs mediate efficient several primary mouse human cell types. Using different glycoproteins alters their cellular tropism. Single injections into mice support therapeutic levels multiple tissues, reducing serum Pcsk9 78% following 63% liver editing, partially restoring visual function a model genetic blindness. In vitro off-target from was virtually undetected, an improvement AAV plasmid delivery. These results establish promising vehicles for macromolecule combine key both viral nonviral

Language: Английский

Citations

415

Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities DOI
Sarah J. Tabrizi, Michael Flower, Christopher A. Ross

et al.

Nature Reviews Neurology, Journal Year: 2020, Volume and Issue: 16(10), P. 529 - 546

Published: Aug. 14, 2020

Language: Английский

Citations

400

Next-generation regulatory T cell therapy DOI
Leonardo M. R. Ferreira, Yannick D. Müller, Jeffrey A. Bluestone

et al.

Nature Reviews Drug Discovery, Journal Year: 2019, Volume and Issue: 18(10), P. 749 - 769

Published: Sept. 20, 2019

Language: Английский

Citations

391

Therapeutic in vivo delivery of gene editing agents DOI Creative Commons
Aditya Raguram, Samagya Banskota, David R. Liu

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(15), P. 2806 - 2827

Published: July 1, 2022

In vivo gene editing therapies offer the potential to treat root causes of many genetic diseases. Realizing promise therapeutic in requires ability safely and efficiently deliver agents relevant organs tissues vivo. Here, we review current delivery technologies that have been used enable editing, including viral vectors, lipid nanoparticles, virus-like particles. Since no single modality is likely be appropriate for every possible application, compare benefits drawbacks each method highlight opportunities future improvements.

Language: Английский

Citations

297

Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy DOI Creative Commons
Ying Gong, Roel G. J. Klein Wolterink, Jianxiang Wang

et al.

Journal of Hematology & Oncology, Journal Year: 2021, Volume and Issue: 14(1)

Published: May 1, 2021

Abstract Due to their efficient recognition and lysis of malignant cells, natural killer (NK) cells are considered as specialized immune that can be genetically modified obtain capable effector for adoptive cellular treatment cancer patients. However, biological technical hurdles related gene delivery into NK have dramatically restrained progress. Recent technological advancements, including improved cell expansion techniques, chimeric antigen receptors (CAR), CRISPR/Cas9 editing enhanced viral transduction electroporation, endowed comprehensive generation characterization cells. These promising developments assist scientists physicians design better applications in clinical therapy. Notably, redirecting using CARs holds important promise immunotherapy. Various preclinical a limited number studies CAR-NK show results: elimination target without side effects, such cytokine release syndrome neurotoxicity which seen CAR-T therapies. In this review, we focus on the details technology, safe CAR constructs associated engineering techniques: vehicles deliver CAR-containing transgene, detection methods CARs, well sources expansion. We summarize current literature include valuable lessons learned from field. This review also provides an outlook how these approaches may transform products protocols treatment.

Language: Английский

Citations

255

Adenoviral vector vaccine platforms in the SARS-CoV-2 pandemic DOI Creative Commons

Samir Andrade Mendonça,

Réka Lőrincz, Paul J. Rice-Boucher

et al.

npj Vaccines, Journal Year: 2021, Volume and Issue: 6(1)

Published: Aug. 5, 2021

Abstract Adenoviral vectors have been explored as vaccine agents for a range of infectious diseases, and their ability to induce potent balanced immune response made them logical candidates apply the COVID-19 pandemic. The unique molecular characteristics these enabled rapid development vaccines with advanced designs capable overcoming biological challenges faced by early adenoviral vector systems. These successes urgency situation resulted in flurry candidate from both academia industry. represent some lead currently supported Operation Warp Speed other government agencies translational development. This review details human clinical trials provides an overview new technologies employed design. As formed cornerstone global vaccination campaign, this full consideration impact emerging platform.

Language: Английский

Citations

254

Next-generation stem cells — ushering in a new era of cell-based therapies DOI
Erin A. Kimbrel, Robert Lanza

Nature Reviews Drug Discovery, Journal Year: 2020, Volume and Issue: 19(7), P. 463 - 479

Published: April 6, 2020

Language: Английский

Citations

234

Nucleic acid delivery for therapeutic applications DOI
Akash Gupta,

Jason L. Andresen,

Rajith S. Manan

et al.

Advanced Drug Delivery Reviews, Journal Year: 2021, Volume and Issue: 178, P. 113834 - 113834

Published: Sept. 4, 2021

Language: Английский

Citations

228

Recent Advances in miRNA Delivery Systems DOI Creative Commons
Ishani Dasgupta, Anushila Chatterjee

Methods and Protocols, Journal Year: 2021, Volume and Issue: 4(1), P. 10 - 10

Published: Jan. 20, 2021

MicroRNAs (miRNAs) represent a family of short non-coding regulatory RNA molecules that are produced in tissue and time-specific manner to orchestrate gene expression post-transcription. MiRNAs hybridize target mRNA(s) induce translation repression or mRNA degradation. Functional studies have demonstrated miRNAs engaged virtually every physiological process and, consequently, miRNA dysregulations been linked multiple human pathologies. Thus, mimics anti-miRNAs restore downregulate aberrantly expressed miRNAs, respectively, highly sought-after therapeutic strategies for effective manipulation levels. In this regard, carrier vehicles facilitate proficient safe delivery miRNA-based therapeutics fundamental the clinical success these pharmaceuticals. Here, we highlight strengths weaknesses current state-of-the-art viral non-viral systems provide perspective on how tools can be exploited improve outcomes therapeutics.

Language: Английский

Citations

226

Engineering living therapeutics with synthetic biology DOI

Andrés Cubillos-Ruiz,

Tingxi Guo, Anna Sokolovska

et al.

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 20(12), P. 941 - 960

Published: Oct. 6, 2021

Language: Английский

Citations

223