Papers, explained in our own words

49. Attachment of Cell-Binding Ligands to Arginine-Rich Cell-Penetrating Peptides Enables Cytosolic Translocation of Complexed siRNA

Skye Zeller, Chang Seon Choi, Pradeep D. Uchil, Hong-Seok Ban, Alyssa Siefert, Tarek M. Fahmy, Walther Mothes, Sang-Kyung Lee, Priti Kumar

Arginine-rich cell-penetrating peptides (CPPs) such as nona-arginine (9R) can effectively translocate covalently attached biomolecules into cells, but poorly deliver electrostatically complexed siRNA, with most CPP:siRNA complexes trapped in endosomes. The mechanism by which ligand attachment to 9R overcomes this…

• siRNA
• Peptides
• Cell-penetrating peptides
• T cells
• Transfection
• mRNA
• Polymeric

50. Dynamin 2-dependent endocytosis sustains T-cell receptor signaling and drives metabolic reprogramming in T lymphocytes

Tim Willinger, Matthew Staron, Shawn M. Ferguson, Pietro De Camilli, Richard A. Flavell

Prolonged T-cell receptor (TCR) signalling is required for T lymphocyte proliferation, yet TCR ligation paradoxically causes internalisation and down-modulation of the TCR from the cell surface. It is unknown how TCR signalling is sustained for many hours despite lower surface expression. Understanding whether TCR…

• T cells
• Endocytosis
• TCR signalling
• mRNA
• Polymeric
• DNA
• Nanocarriers

51. Targeting nanoparticles to CD40, DEC-205 or CD11c molecules on dendritic cells for efficient CD8+ T cell response: A comparative study

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…

• T cells
• Nanoparticles
• Dendritic cells
• PLGA
• Biodistribution
• Polymeric
• Targeted delivery

52. Liposome-Coated Lipoplex-Based Carrier for Antisense Oligonucleotides

Paulina Wyrozumska, Justyna Meissner, Monika Toporkiewicz, Marta Szarawarska, Kazimierz Kuliczkowski, Maciej Ugorski, Marta A. Walasek & Aleksander F. Sikorski

Most cancer gene therapy research has focused on solid tumours, while blood cancers such as leukaemia and lymphoma have received less attention. There is a need for a lipid carrier that protects antisense oligonucleotides or plasmid DNA from enzymatic degradation, is stable in serum, has low toxicity, and can…

• Transfection
• DNA
• Biodistribution
• Liposomes
• mRNA
• Nucleic acids
• T cells

53. A Carbon Nanotube–Polymer Composite for T-Cell Therapy

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…

• T cells
• Polymeric
• Nanoparticles
• PLGA
• Cancer immunotherapy
• Dendritic cells
• Antigen presentation

54. GM-CSF-loaded chitosan hydrogel as an immunoadjuvant enhances antigen-specific immune responses with reduced toxicity

Kyung Hee Noh, Yeong Min Park, Hyuk Soon Kim, Tae Heung Kang, Kwon‐ho Song, Young‐ho Lee, Yeongseon Byeon, Hat Nim Jeon, In Duk Jung, Byung Cheol Shin, Kyung‐mi Lee, Seung‐yong Seong, Hee Dong Han, Tae Woo Kim

Conventional adjuvants such as Complete Freund’s Adjuvant (CFA) and Incomplete Freund’s Adjuvant (IFA) are potent but toxic, limiting clinical use. A safer, biodegradable adjuvant system was needed to enhance antigen-specific humoral and cellular immunity without severe local or systemic side effects. Safety: CH-HG…

• Chitosan
• T cells
• Polymeric
• Nanocarriers
• Gene delivery
• Drug delivery
• Nanoparticles

55. Potential of Ni(II)-NTA-Modified Poly(ethylene imine) Glycopolymers as Carrier System for Future Dendritic Cell-Based Immunother

Hauptmann N, Pion M, Wehner R, Muñoz-Fernández M-A, Schmitz M, Voit B, Appelhans D

Dendritic cell (DC)-based immunotherapy requires efficient delivery of antigens to immature DCs (iDCs) and maintenance of their immunostimulatory and migratory functions. Cationic PEI carriers are limited by dose-dependent toxicity and aggregation at endosomal pH, so a biocompatible, pH-responsive carrier is needed…

• Polymeric
• Polyethylenimine
• T cells
• Antigen presentation
• Nanocarriers
• Gene delivery
• Drug delivery

56. PLGA-nanoparticle mediated delivery of anti-OX40 monoclonal antibody enhances anti-tumor cytotoxic T cell responses

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…

• T cells
• PLGA
• Nanoparticles
• Polymeric
• Cancer immunotherapy
• Dendritic cells
• Antigen presentation

57. An Efficient Low Cost Method for Gene Transfer to T Lymphocytes

Lais Chayabam, Aline Laino Sodre, Bruno A. Curzio, Martin H. Bonamino

Genetic modification of T lymphocytes is essential for both basic research and immunotherapy (e.g., CAR-T cell generation), but existing methods rely on expensive commercial electroporation kits (Lonza Nucleofector® kits) or time-consuming viral vector production. The high cost and dependence on proprietary reagents…

• T cells
• Transfection
• Polymeric
• DNA
• CAR-T cells
• Nanocarriers
• Gene delivery

58. Selective Activation of Antigen-Experienced T Cells by Anti-CD3 Constrained on Nanoparticles

Ying-Chun Lo, Michael A. Edidin, Jonathan D. Powell

Soluble anti-CD3 antibodies are potent T cell mitogens but activate all T cells regardless of TCR specificity, limiting their therapeutic utility for boosting antigen-specific responses. TCRs cluster into microclusters on the surface of antigen-experienced T cells but remain dispersed on naive T cells. This…

• T cells
• Nanoparticles
• TCR signalling
• Immune cells
• Nanocarriers
• Gene delivery
• Drug delivery

59. Optimization of encapsulation of a synthetic long peptide in PLGA nanoparticles: low burst release is crucial for efficient CD8⁺ T cell activation

A.L. Silva, R.A. Rosalia, A. Sazak, M.G. Carstens, F. Ossendorp, J. Oostendorp, W. Jiskoot

Overlapping synthetic long peptides (SLPs) are promising for therapeutic cancer vaccination, but Montanide-based formulations have limitations including non-biodegradability, local side effects, poorly controlled release, and limited scalability. PLGA nanoparticles (NPs) offer a biodegradable alternative, but…

• T cells
• PLGA
• Nanoparticles
• Antigen presentation
• Controlled release
• Peptides
• Polymeric

60. Lipid-derived nanoparticles for immunostimulatory RNA adjuvant delivery

David N. Nguyen, Kerry P. Mahon, Ghania Chikh, Phillip Kim, Hattie Chung, Alain P. Vicari, Kevin T. Love, Michael Goldberg, Steve Chen, Arthur M. Krieg, Jianzhu Chen, Robert Langer, Daniel G. Anderson

TLR7/8 agonists are promising vaccine adjuvants and antivirals, but RNA agonists are unstable and small-molecule agonists cause systemic toxicity. A delivery system specifically designed to deliver immunostimulatory RNA (isRNA) to TLR-expressing cells could enable safer and more localised innate immune activation. 14…

• Nanoparticles
• T cells
• Nanocarriers
• Gene delivery
• Drug delivery
• Immune cells
• Transfection

61. Polymer Nanoparticles Containing Tumor Lysates as Antigen Delivery Vehicles for Dendritic Cell–Based Antitumor Immunotherapy

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…

• Nanoparticles
• Polymeric
• T cells
• PLGA
• Dendritic cells
• Nanocarriers
• Gene delivery

62. Activation of Antigen-Specific T Cell-Responses by Mannan-Decorated PLGA Nanoparticles

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…

• T cells
• PLGA
• Nanoparticles
• Polymeric
• Dendritic cells
• Vaccine delivery
• Peptides

63. Cancer gene therapy by IL-12 gene delivery using liposomal bubbles and tumoral ultrasound exposure

IL-12 gene therapy is attractive for cancer because local IL-12 expression can prime anti-tumour immunity while reducing systemic toxicity. However, non-viral gene delivery to tumours is inefficient, and simple sonoporation using ultrasound alone does not achieve sufficient cancer gene therapy. The authors tested…

• Gene delivery
• Liposomes
• T cells
• mRNA
• DNA
• Transfection
• Nanocarriers

64. Chitosan hydrogel containing GMCSF and a cancer drug exerts synergistic anti-tumor effects via the induction of CD8+ T cell-mediated anti-tumor immunity

Seo Sh, Han Hd, Noh Kh, Kim Tw, Son Sw

Chemo-immunotherapy combinations are limited by systemic immunotoxicity from cancer drugs and rapid clearance of low-molecular-weight drugs after intratumoral injection. A local, biodegradable delivery system was needed to sustain drug/GMCSF exposure at the tumour site, reduce systemic toxicity, and promote tumour…

• T cells
• Chitosan
• Nanocarriers
• Gene delivery
• Drug delivery
• Nanoparticles
• Immune cells

65. Targeted PLGA nano- but not microparticles specifically deliver antigen to human dendritic cells via DC-SIGN in vitro

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…

• PLGA
• Dendritic cells
• T cells
• Antigen presentation
• Nanoparticles
• Polymeric
• Vaccine delivery

66. MRI-Visible Polymeric Vector Bearing CD3 Single Chain Antibody for Gene Delivery to T Cells for Immunosuppression

Chen Guihua, Chen Wenjie, Wu Zhuang, Yuan Renxu, Li Hua, Gao Jinming, Shuai Xintao

Gene therapy could induce immunosuppression with greater durability and less toxicity than conventional agents like cyclosporine A, but T cells are notoriously refractory to non-viral gene delivery. An effective, T-cell-targeted, MRI-trackable non-viral vector is needed for immunosuppression in transplantation and…

• Polymeric
• T cells
• Gene delivery
• Transfection
• Polyethylenimine
• DNA
• Endocytosis

67. Co-delivery of cancer-associated antigen and Toll-like receptor 4 ligand in PLGA nanoparticles induces potent CD8⁺ T cell-mediated anti-tumor immunity

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…

• T cells
• PLGA
• Nanoparticles
• Tumour microenvironment
• Polymeric
• Dendritic cells
• Nanocarriers

68. Polymer Nanoparticles for Immunotherapy from Encapsulated Tumor-Associated Antigens and Whole Tumor Cells

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…

• Nanoparticles
• Polymeric
• T cells
• PLGA
• Dendritic cells
• Antigen presentation
• Nanocarriers

69. Selective targeting of antibody-conjugated nanoparticles to leukemic cells and primary T-lymphocytes

Norbert Dinauer, Sabine Balthasar, Carolin Weber, Jörg Kreuter, Klaus Langer, Hagen Von Briesen

Antibody-based therapeutics have shown promise in targeting specific cell types, but their efficacy can be enhanced by conjugation to drug carriers. Nanoparticles as drug carriers offer advantages including high drug loading capacity, controlled release, and protection from degradation. However, achieving selective…

• Nanoparticles
• T cells
• Endocytosis
• Cellular uptake
• Drug delivery
• Targeted delivery
• Controlled release

70. Receptor-mediated gene delivery to human peripheral blood mononuclear cells using anti-CD3 antibody coupled to polyethylenimine

Primary lymphoid cells, especially human peripheral blood mononuclear cells (PBMC), are very difficult to transfect with viral and nonviral vectors. There is a need for efficient nonviral, receptor-mediated gene delivery to PBMC for cell-based therapies and for studying gene function in primary lymphocytes. Naive vs…

• Polyethylenimine
• Gene delivery
• Transfection
• DNA
• Polymeric
• Viral vectors
• T cells

71. Internalization and Cycling of the T Cell Antigen Receptor - Role of Protein Kinase C

Yasuhiro Minami, Lawrence E. Samelson, Richard D. Klausner

The T cell antigen receptor (TCR) plays a critical role in T cell activation, but the dynamics of TCR internalisation and its regulation were poorly understood. It was known that phorbol esters (activators of protein kinase C) lead to loss of surface TCRs, but the mechanisms—whether internalisation was…

• T cells
• TCR signalling
• Nanocarriers
• Gene delivery
• Drug delivery
• Nanoparticles
• Immune cells

72. Endocytosis in Cytotoxic T-Lymphocytes

Hans-Jörg Heiniger, Arnold Sodergren, Jan D. Marshall

While pinocytosis (endocytosis) in lymphocytes had been qualitatively described using electron microscopy, quantitative measurements of endocytic activity and its relationship to immunological function were lacking. Understanding whether endocytosis correlates with T cell differentiation and cytotoxic function is…

• Endocytosis
• T cells
• Macrophages
• Nanocarriers
• Gene delivery
• Drug delivery
• Nanoparticles