A5066683314- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- 3D Printing in Biomedical Research
- Angiogenesis and VEGF in Cancer
- T-cell and B-cell Immunology
- Hydrogels: synthesis, properties, applications
- Immune cells in cancer
- vaccines and immunoinformatics approaches
- RNA Interference and Gene Delivery
- Peripheral Artery Disease Management
- interferon and immune responses
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Coronary Interventions and Diagnostics
- Blood disorders and treatments
- Hematopoietic Stem Cell Transplantation
- Cellular Mechanics and Interactions
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Neutropenia and Cancer Infections
- Virus-based gene therapy research
- Bacterial Infections and Vaccines
- Platelet Disorders and Treatments
- Extracellular vesicles in disease
- Immune Response and Inflammation
- Tissue Engineering and Regenerative Medicine
Harvard University
2016-2023
Harvard University Press
2021
Immunotherapy has had a tremendous impact on cancer treatment in the past decade, with hitherto unseen responses at advanced and metastatic stages of disease. However, aggressive brain tumor glioblastoma (GBM) is highly immunosuppressive remains largely refractory to current immunotherapeutic approaches. The stimulator interferon genes (STING) DNA sensing pathway emerged as next-generation immunotherapy target potent local immune stimulatory properties. Here, we investigated status STING GBM...
Abstract Although adoptive T cell therapy provides the pool needed for immediate tumor debulking, infused cells generally have a narrow repertoire antigen recognition and limited ability long-term protection. Here, we present hydrogel that locally delivers adoptively transferred to site while recruiting activating host antigen-presenting with GMCSF or FLT3L CpG, respectively. alone loaded into these localized depots provided significantly better control of subcutaneous B16-F10 tumors than...
Abstract Hydrogels are under active development for controlled drug delivery, but their clinical translation is limited by low loading capacity, deficiencies in mechanical toughness and storage stability, poor control over the release that often results burst short duration. This work reports a design of composite clay hydrogels, which simultaneously achieve spectrum mechanical, storage, loading/releasing properties to address critical needs from translational perspectives. The nanoparticles...
Abstract Vaccines have shown significant promise in eliciting protective and therapeutic responses. However, most effective vaccines require several booster shots, it is challenging to generate responses against synthetic molecules peptides often used increase target specificity improve vaccine stability. As continuous antigen uptake processing by antigen‐presenting cells persistent toll‐like receptor priming can amplify humoral immunity, explored whether a single injection of mesoporous...
Targeted subunit vaccines for cancer immunotherapy do not capture tumor antigenic complexity, and approaches employing lysate are often limited by inefficient antigen uptake presentation, low immunogenicity. Here, whole cells processed to generate antigen‐rich, membrane‐enclosed subcellular particles, termed “reduced cells”, that reflect the diversity breadth of parent cell repertoire, can be loaded with disparate adjuvant payloads. These vesicular particles enhance payload, potentiate...
Abstract Traditional bolus vaccines often fail to sustain robust adaptive immune responses, typically requiring multiple booster shots for optimal efficacy. Additionally, these provide few opportunities control the resulting subclasses of antibodies produced, which can mediate effector functions relevant distinct disease settings. Here, it is found that three scaffold‐based vaccines, fabricated from poly(lactide‐ co ‐glycolide) (PLG), mesoporous silica rods, and alginate cryogels, induce...
Abstract The optimal means to prime for effective anti-tumor immunity in a cancer patient remains elusive the current era of checkpoint blockade. Crafting strategy amplify CD8+ T cells while blocking regulatory should increase immunotherapy efficacy. Biomaterial carriers have been demonstrated preclinical studies effects immunomodulatory agents, synergistically integrate different and concentrate manipulate immune vivo. In this phase I trial patients with metastatic melanoma, cytokine GM-CSF...
Biomaterial-based delivery of angiogenic growth factors restores perfusion more effectively than bolus methods in rodent models peripheral vascular disease, but the same success has not yet been demonstrated clinically relevant studies aged or large animals. These explore, models, a therapeutic angiogenesis strategy for treatment disease that overcomes challenges encountered previous clinical trials. Alginate hydrogels providing sustained release endothelial factor (VEGF) and insulin-like...
Neutrophils are essential effector cells for mediating rapid host defense and their insufficiency arising from therapy-induced side-effects, termed neutropenia, can lead to immunodeficiency-associated complications. In autologous hematopoietic stem cell transplantation (HSCT), neutropenia is a complication that limits therapeutic efficacy. Here, we report the development in vivo evaluation of an injectable, biodegradable hyaluronic acid (HA)-based scaffold, HA cryogel, with myeloid...
Abstract Immunotherapy has had a tremendous impact on cancer treatment in the past decade, with hitherto unseen responses at advanced and metastatic stages of disease. However, aggressive brain tumor glioblastoma (GBM) is highly immunosuppressive remains largely refractory to current immunotherapeutic approaches. The cGAS-STING cytoplasmic double stranded DNA (dsDNA) sensing pathway emerged as next-generation immunotherapy target potent local immune stimulatory properties. Here, we...
Abstract Bypass graft failure occurs in 20%–50% of coronary and lower extremity bypasses within the first‐year due to intimal hyperplasia (IH). TSP‐2 is a key regulatory protein that has been implicated development IH following vessel injury. In this study, we developed biodegradable CLICK‐chemistry gelatin‐based hydrogel achieve sustained perivascular delivery siRNA rat carotid arteries endothelial denudation At 21 days, application embedded hydrogels significantly downregulated gene...
Abstract Broad spectrum vaccines could provide a solution to the emergence of antibiotic resistant microbes, pandemics and engineered biothreat agents. Here, we describe modular vaccine (composite infection technology (ciVAX)) which can be rapidly assembled in 4 5 components are already approved for human use. ciVAX consists an injectable biomaterial scaffold with factors recruit activate dendritic cells (DC) vivo microbeads conjugated broad-spectrum opsonin Fc-Mannose-binding Lectin (FcMBL)...
Abstract Vaccines have shown significant promise in eliciting protective and therapeutic responses. However, most effective vaccines require several booster shots, it is challenging to generate potent responses against small molecules synthetic peptide antigens often used increase target specificity improve vaccine stability. As continuous antigen uptake processing by APCs persistent toll-like receptor (TLR) priming been amplify specific humoral immunity, we explored whether a single...
Abstract Adoptive T cell therapy provides the pool needed for immediate tumor debulking, but infused cells generally have a narrow repertoire antigen recognition and limited ability long-term protection. Here, we present biomaterial platform that enhances adoptive by synergistically engaging host immune system via in-situ antigen-free vaccination. alone loaded into these localized depots provided significantly better control of subcutaneous B16-F10 tumors than delivered through direct...
Abstract There is an urgent need to develop vaccines against bacteria due the rise of Multi-drug resistant (MDR & XDR) organisms. To date, it has been difficult produce protective bacterial pathogens; there a danger outgrowth fast growing attenuated strains while polysaccharide cell walls are poorly immunogenic and subunit ineffective, generating TI (T-independent) immune responses, characterized by low affinity, short lived, non-class switched IgM antibodies. We developing technologies...