A5060222591- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Nanowire Synthesis and Applications
- Click Chemistry and Applications
- Immune Cell Function and Interaction
- Chemical Synthesis and Analysis
- Viral gastroenteritis research and epidemiology
- Integrated Circuits and Semiconductor Failure Analysis
- Cancer Research and Treatments
- Animal Virus Infections Studies
- Viral Infectious Diseases and Gene Expression in Insects
- 3D Printing in Biomedical Research
- Tissue Engineering and Regenerative Medicine
- Pluripotent Stem Cells Research
- Cytomegalovirus and herpesvirus research
- Nanoparticle-Based Drug Delivery
- Antimicrobial Peptides and Activities
- Immunodeficiency and Autoimmune Disorders
- Toxin Mechanisms and Immunotoxins
- HIV Research and Treatment
- Advanced biosensing and bioanalysis techniques
- Biosimilars and Bioanalytical Methods
- Graphene and Nanomaterials Applications
Hartford Financial Services (United States)
2024
Advanced Cell Technology (United States)
2021
University of Pennsylvania
2017
University of Southern California
2009-2016
California NanoSystems Institute
2009
University of California, Los Angeles
2009
University of Science and Technology of China
2009
Hefei National Center for Physical Sciences at Nanoscale
2009
The effects of transgenically encoded human and mouse IL-18 on T cell proliferation its application in boosting chimeric antigen receptor (CAR) cells are presented. Robust enhancement IL-18-secreting occurred a xenograft model, this was dependent TCR IL-18R signaling. augmented IFN-γ secretion activated by the endogenous TCR. TCR-deficient, IL-18-expressing CD19 CAR exhibited enhanced antitumor activity model. Antigen-propelled activation cytokine helper ensemble (APACHE) displayed inducible...
Target proteins can be functionally encapsulated using a cocoon-like polymeric nanocapsule formed by interfacial polymerization. The is cross-linked peptides that proteolyzed proteases upon which the protein cargo released. protease-mediated degradation process controlled in spatiotemporal fashion through modification of peptide cross-linker with photolabile moieties. We demonstrate utility this approach cytoplasmic delivery apoptosis inducing caspase-3 to cancer cells.
Attempts to develop cell-based cancer vaccines have shown limited efficacy, partly because transplanted dendritic cells (DCs) do not survive long enough reach the lymph nodes. The development of biomaterials capable modulating DCs in situ enhance antigen uptake and presentation has emerged as a novel method toward developing more efficient vaccines. Here, we propose two-step hybrid strategy produce robust vaccine situ. First, significant number are recruited an injectable thermosensitive...
Peptides constructed with the 20 natural amino acids are generally considered to have little therapeutic potential because they unstable in presence of proteases and peptidases. However, proteolysis cleavage can be idiosyncratic it is possible that analogues functional sequences exist highly resistant cleavage. Here, we explored this idea context peptides bind signaling protein Gαi1. To do this, used a two-step vitro selection process simultaneously select for protease resistance while...
Abstract IL6 is one of the most elevated cytokines during chimeric antigen receptor (CAR) T cell cytokine release syndrome (CRS), and IL6R blockade by Tocilizumab has successfully relieved life-threatening aspects CRS in patients. In addition, latest studies demonstrated essential role IL1 driving CART induced neurotoxicity mouse models. Here we present a clinical investigation (ChiCTR2000032124; ChiCTR2000031868) anti-CD19 anti-BCMA (41BBζ) secreting an anti-IL6 scFv antagonist (IL1RA)...
Abstract Revolutionary CART therapy still faces the challenge of severe cytokine release syndrome (CRS). While IL6 and IL1 have been demonstrated as essential contributors, GM-CSF is one most abundant inflammatory cytokines secreted by has also suggested in contributing to CRS. To minimize production from reduce its associated toxicity, we conducted a pilot study (ChiCTR2000032124) CRISPR-edited knockout (KO) secreting anti-IL6 scFv IL1RA, with additional TCR KO for tracing edited CART. The...
Lentivectors (LVs) have attracted considerable interest for their potential as a vaccine delivery vehicle. In this study, we evaluate in mice dendritic cell (DC)-directed LV system encoding the Gag protein of human immunodeficiency virus (HIV) (LV-Gag) inducing an anti-HIV immune response. The DC-directed specificity is achieved through pseudotyping vector with engineered Sindbis glycoprotein capable selectively binding to DC-SIGN protein. A single immunization by induces durable HIV...
A therapeutically effective cancer vaccine must generate potent antitumor immune responses and be able to overcome tolerance mechanisms mediated by the progressing tumor itself. Previous studies showed that glycoprotein 100 (gp100), tyrosinase-related protein 1 (TRP1), 2 (TRP2) are promising immunogens for melanoma immunotherapy. In this study, we administered these three melanoma-associated antigens via lentiviral vectors (termed LV-3Ag) found multi-antigen strategy markedly increased...
Abstract Peptides typically have poor biostabilities, and natural sequences cannot easily be converted into drug‐like molecules without extensive medicinal chemistry. We adapted mRNA display to drive the evolution of highly stable cyclic peptides while preserving target affinity. To do this, we incorporated an unnatural amino acid in library that was subjected proteolysis prior selection for function. The resulting “SUPR (scanning protease resistant) peptide” showed ≈500‐fold improvement...
We describe a FRET-based protease detection strategy, using single-fluorescent-protein nanogel as donor and dark quencher acceptor linked by photolabile caged-peptide. This design enables probing of activity in UV-responsive fashion.
It has been demonstrated that nonintegrating lentiviral vectors (NILVs) are efficient in maintaining transgene expression vitro and vivo. Gene delivery by NILVs can significantly reduce nonspecific vector integration, which shown to cause malignant transformation patients receiving gene therapy for X-linked severe combined immunodeficiency. Strong sustained immune responses were observed after a single immunization with carrying viral antigens. However, there is no report date evaluates the...
Abstract The unique self‐renewal and pluripotency features of human embryonic stem cells (hESCs) offer the potential for unlimited development novel cell therapies. Currently, hESCs are cultured differentiated using methods, such as monolayer culture embryoid body (EB) formation. As such, achieving efficient differentiation into higher order structures remains a challenge, well maintaining viability during homogeneous populations. Here, we describe application highly porous polymer scaffolds...
Lentiviral vectors (LVs) are promising delivery systems for gene therapy, and they can be further engineered to increase their potential effectively delivering transgenes desired cell populations. Here, we have LVs pseudotyped with envelope glycoproteins derived from lymphocytic choriomeningitis virus (LCMV) antigen elicit vaccine-directed immune responses. Two variants, LCMV-WE LCMV-Arm53b, were evaluated ability mediate LV-based cellular transduction in vitro. a leucine residue at position...
Abstract Interleukin 18 (IL18) is known to induce the expression of interferon-γ (IFNG), but its effects on T cell proliferation and costimulation are not completely understood. In this study, we demonstrate that ectopic IL18 in CART cells caused significant vitro vivo, enhanced antitumor xenograft models. Moreover, mediated expansion required neither tumor antigen nor CAR expression, produced severe GVHD NSG mice. Furthermore, recombinant costimulated IFNG secretion anti-CD3 beads treated...
2502 Background: CART cells have demonstrated remarkable clinical efficacy in treating hematological cancers. However, CRS remains as a major challenge application, with multiple cytokines significantly elevated. IL6 signaling blockade by Tocilizumab has become standard treatment to relieve patients. Our previous studies suggested that CAR T secreting antagonist could effectively maintain at very low levels during CRS. Furthermore, we observed huge quantity of tumor one patient was reduced...
Abstract Virtually all human cancer cells have elaborate anti-apoptotic strategies to overcome apoptosis, including inactivation of the p53 pathway and hyperactivation NF-κB. Therefore, ability rapidly resurrect apoptosis in tumor can be an effective option for treatment. Although different been developed counter individual mechanisms, a more potent chemotherapy is directly arm with apoptosis-inducing proteins. From therapeutic perspective, protein-based approaches are safer than gene...