Science Advances2022ResearchNon-viral Gene Delivery
Rasheid Smith, Emad I. Wafa, Sean M. Geary, Kareem Ebeid, Suhaila O. Alhaj-Suliman, Aliasger K. Salem
Cancer vaccines as monotherapies have displayed limited clinical success due to the immunosuppressive tumour microenvironment (TME). Nanoscale formulations can enhance vaccine efficacy by combating TME immunosuppression, but there is a need for novel adjuvant formulations that can be combined with therapeutic cancer…
Read the article →Angewandte Chemie International Edition2020ResearchNon-viral Gene Delivery
Xuewei Zhao, Jinjin Chen, Min Qiu, Yamin Li, Zachary Glass, Qiaobing Xu
In vivo engineering of T lymphocytes is limited by poor transfection efficiency and reliance on ex vivo electroporation. A non-viral mRNA delivery platform that can target primary T cells in vivo is needed for CAR T-cell therapy, vaccines, and immunotherapy. Rough screening identified imidazole head 93 with O17O…
Read the article →International Journal of Pharmaceutics2018ReviewNon-viral Gene Delivery
Tran Th, Tran Ttp, Nguyen Ht, Phung Cd, Jeong J-H, Stenzel Mh, Jin Sg, Yong Cs, Truong Dh, Kim Jo.
Dendritic cell (DC)-based cancer immunotherapy is promising but limited by poor antigen immunogenicity, weak stability, and short in vivo half-life. Nanotechnology can protect antigens and adjuvants from premature degradation, enhance delivery to DCs, and improve therapeutic T cell responses. This review summarises…
Read the article →Biomaterials2017ResearchNon-viral Gene Delivery
Yoshizaki Y, Yuba E, Sakaguchi N, Koiwai K, Harada A, Kono K
Efficient cancer vaccine carriers need both antigen delivery to dendritic cells (DCs) and DC activation. Previous pH-sensitive polymer-modified liposomes delivered antigen to DC cytosol but had limited adjuvant potency, and combining cationic lipid TRX with MPLA reduced antitumor effects, suggesting a need for…
Read the article →Biomaterials2017ResearchNon-viral Gene Delivery
Shi Gn, Zhang Cn, Xu R, Niu Jf, Song Hj, Zhang Xy, Wang Ww, Wang Ym, Li C, Wei Xq, Kong Dl
Whole tumour cell lysates (TCL) are a broad source of tumour antigens for cancer vaccines, but soluble TCL is unstable, poorly taken up by dendritic cells (DCs), and inefficient at inducing cytotoxic T lymphocyte (CTL) responses. A delivery system was needed to protect TCL antigens, target DCs, and enhance antigen…
Read the article →Nanoscale2016ResearchNon-viral Gene Delivery
Joshua J. Glass, Daniel Yuen, James Rae, Angus P. R. Johnston, Robert G. Parton, Stephen J. Kent, Robert De Rose
Investigations of nanoparticle targeting to immune cells are conventionally restricted to monocultured cell line models that lack the complexity of primary human blood cell populations, including non-specific association with, and competition from, diverse cell types. A more physiologically relevant system using…
Read the article →Molecular Therapy2016ResearchNon-viral Gene Delivery
Ans De Beuckelaer, Charlotte Pollard, Sandra Van Lint, Kenny Roose, Lien Van Hoecke, Thomas Naessens, Vimal Kumar Udhayakumar, Muriel Smet, Niek Sanders, Stefan Lienenklaus, Xavier Saelens, Siegfried Weiss, Guido Vanham, Johan Grooten & Stefaan De Koker
mRNA vaccines are promising for inducing cytolytic CD8⁺ T cell responses, and lipoplex carriers improve mRNA delivery to dendritic cells. However, the innate factors that regulate T cell induction by mRNA lipoplex vaccines remain unresolved. In particular, type I interferons (IFNs) are induced by mRNA but can either…
Read the article →ACS Nano (Just Accepted Manuscript)2015ResearchNon-viral Gene Delivery
Jian Xiang, Ligeng Xu, Hua Gong, Wenwen Zhu, Chao Wang, Jun Xu, Liangzhu Feng, Liang Cheng, Rui Peng, Zhuang Liu
Dendritic cell (DC)-based immunotherapy requires efficient antigen delivery into DCs, DC maturation, and migration to draining lymph nodes, but real-time tracking of DC migration remains challenging with traditional methods (e.g., FITC painting). While upconversion nanoparticles (UCNPs) offer advantages for sensitive…
Read the article →Biomaterials2014ResearchNon-viral Gene Delivery
Luis J. Cruz, Rodney A. Rosalia, Jan Willem Kleinovink, Felix Rueda, Clemens W.G.M. Löwik, Ferry Ossendorp
Dendritic cell (DC)-based therapies have shown clinical benefits but are hampered by labour-intensive, GMP-regulated vaccine preparations requiring multiple steps and donor variability. In vivo targeting of antigens to DC surface receptors using nanoparticle delivery systems could circumvent these drawbacks. However…
Read the article →Nature Nanotechnology2014ResearchNon-viral Gene Delivery
Tarek R. Fadel, Fiona A. Sharp, Nalini Vudattu, Ragy Ragheb, Justin Garyu, Dongin Kim, Enping Hong, Nan Li, Gary L. Haller, Lisa D. Pfefferle, Sune Justesen, Kevan C. Herold, Tarek M. Fahmy
Adoptive cell transfer of tumour-specific T cells is a promising cancer immunotherapy, but efficient and economical ex vivo expansion of T cells remains a bottleneck. Artificial antigen-presenting cells (aAPCs) with high surface area and modular design could overcome cost and scalability limits of dendritic…
Read the article →Cellular Immunology (Elsevier)2014ResearchNon-viral Gene Delivery
Mingshui Chen, Haichao Ouyang, Shangyong Zhou, Jieyu Li, Yunbin Ye
Agonistic anti-OX40 monoclonal antibody (mAb) can enhance anti-tumour immunity in preclinical models, but as monotherapy it showed only marginal activity and no objective clinical responses in a phase I trial. A delivery system that improves T cell access, multivalent OX40 engagement, and sustained release of…
Read the article →Current Opinion in Lipidology2012ReviewNon-viral Gene Delivery
Vickers Kc, Remaley At
Extracellular miRNAs are unusually stable in plasma and their circulating levels change with disease, making them promising biomarkers. They are associated with lipid-based carriers—exosomes, microvesicles, apoptotic bodies, and lipoproteins—as well as lipid-free proteins. Whether these carriers mediate functional…
Read the article →Nanomedicine: Nanotechnology, Biology, and Medicine2011ResearchNon-viral Gene Delivery
Shashi Prasad, Virginia Cody, Jennifer K. Saucier-Sawyer, W. Mark Saltzman, Clarence T. Sasaki, Richard L. Edelson, Martin A. Birchall, Douglas J. Hanlon
Efficient antigen delivery remains a major challenge for dendritic cell (DC)-based immunotherapy of solid-organ malignancies. Soluble tumour lysates suffer from instability, poor DC internalisation, and inefficient cross-presentation to cytotoxic T lymphocytes. PLGA nanoparticles may protect antigens, improve…
Read the article →Pharmaceutical Research2011ResearchNon-viral Gene Delivery
Samar Hamdy, Azita Haddadi, Anooshirvan Shayeqanpour, John Samuel, Afsaneh Lavasanifar
Mannosylation of vaccine formulations is a promising strategy to target antigens to the mannose receptor (MR) on dendritic cells (DCs), potentially improving antigen uptake, processing, and presentation. While PLGA nanoparticles (NPs) are established vaccine delivery vehicles, the effect of chemical conjugation of…
Read the article →Journal of Controlled Release2010ResearchNon-viral Gene Delivery
Luis J. Cruz, Paul J. Tacken, Remco Fokkink, Ben Joosten, Martien Cohen Stuart, Fernando Albericio, Ruurd Torensma, Carl G. Figdor
Antibody-mediated targeting of vaccine components to dendritic cells (DCs) enhances vaccine efficacy, but linking multiple antigens and immune modulators to a single antibody is limited. Slow-release PLGA particles conjugated to DC-specific antibodies could overcome this by delivering large antigen payloads and…
Read the article →Advanced Materials2009ResearchNon-viral Gene Delivery
Joel Sunshine, Jordan J. Green, Kerry P. Mahon, Fan Yang, Ahmed A. Eltoukhy, David N. Nguyen, Robert Langer, Daniel G. Anderson
Viral vectors are efficient but face safety, manufacturing, and cargo-capacity limitations. Cationic polymers such as poly(β-amino ester)s (PBAEs) are promising non-viral alternatives, but their gene delivery efficacy varies across cell types. The study asked whether small-molecule end groups on a linear PBAE could…
Read the article →Vaccine2008ResearchNon-viral Gene Delivery
S. Hamdy, O. Molavi, Z. Ma, A. Haddadi, A. Alshamsan, Z. Gobti, S. Elhasi, J. Samuel, A. Lavasanifar
Most PLGA-based cancer vaccine studies used foreign model antigens such as ovalbumin (OVA), which are not subject to central/peripheral tolerance and can overestimate therapeutic efficacy. There is a need to evaluate PLGA vaccines against a realistic, clinically relevant self/tumor antigen (TRP2) and to overcome…
Read the article →Molecular Pharmaceutics2007ResearchNon-viral Gene Delivery
C. M. Solbrig, J. K. Saucier-Sawyer, V. Cody, W. M. Saltzman, D. J. Hanlon
Current antitumor vaccines are limited by the small number of defined tumour-associated antigens (TAAs) for most solid tumours and by poor delivery of soluble antigen to dendritic cells (DCs). Autologous whole-tumour lysates contain the full antigenic repertoire, but soluble lysates are unstable and poorly…
Read the article →Journal of Controlled Release2007ResearchNon-viral Gene Delivery
Xianfeng Zhou, Bin Liu, Xianghui Yu, Xiao Zha, Xizhen Zhang, Yu Chen, Xueyun Wang, Yinghua Jin, Yongge Wu, Yue Chen, Yaming Shan, Yan Chen, Junqiu Liu, Wei Kong, Jiacong Shen
DNA vaccines can induce antibody and CTL responses, but clinical translation is limited by weak potency and the need for high or repeated doses. The study addresses this by targeting DNA to antigen-presenting cells (APCs) and improving endosomal/lysosomal release, using mannose-bearing chitosan microspheres loaded…
Read the article →Journal of Controlled Release2006ResearchNon-viral Gene Delivery
DNA vaccines are limited by inefficient delivery to antigen-presenting cells (APCs) and lack of adjuvant effect, especially for weakly immunogenic self/tumor antigens. The study addresses this by using cationic PEI-functionalised PLGA microparticles to enhance APC activation and protective anti-tumour immunity…
Read the article →Advanced Drug Delivery Reviews2005ReviewNon-viral Gene Delivery
Ying Waeckerle-Men And Marcus Groettrup
Dendritic cell (DC)-based vaccines are limited by the short persistence of MHC class I/peptide complexes on the DC surface—often only a few hours—when soluble peptides are loaded exogenously. This short presentation limits CTL activation and vaccine efficacy. The authors investigated biodegradable PLGA microspheres…
Read the article →Trends in Immunology2002ReviewNon-viral Gene Delivery
James Harris, Dirk Werling, Jayne C. Hope, Geraldine Taylor, Chris J. Howard
Caveolae and caveolin are cholesterol-rich membrane microdomains involved in endocytosis, cholesterol regulation, and signal transduction, but their presence and function in immune cells have been contentious. This review addresses the need to clarify the distribution and roles of caveolae/caveolin in mammalian…
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