A5010856411- Immune cells in cancer
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Glioma Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Cancer Research and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA Interference and Gene Delivery
- T-cell and B-cell Immunology
- Extracellular vesicles in disease
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Chemokine receptors and signaling
- Cancer, Hypoxia, and Metabolism
- SARS-CoV-2 and COVID-19 Research
- 3D Printing in Biomedical Research
- Mesenchymal stem cell research
- Virus-based gene therapy research
Seattle Children's Hospital
2016-2023
University of Washington
2018-2022
Oxford University Press (United Kingdom)
2020
Children’s Institute
2020
Though currently approved immunotherapies, including chimeric antigen receptor T cells and checkpoint blockade antibodies, have been successfully used to treat hematological some solid tumor cancers, many tumors remain resistant these modes of treatment. In tumors, the development effective antitumor immune responses is hampered by restricted cell infiltration an immunosuppressive microenvironment (TME). An immunotherapy that infiltrates persists in TME, while providing local, stable levels...
Abstract Background Most glioblastomas recur near prior radiation treatment sites. Future clinical success will require achieving and optimizing an “abscopal effect,” whereby unirradiated neoplastic cells outside sites are recognized attacked by the immune system. Radiation combined with anti–programmed cell death ligand 1 (PD-L1) demonstrated modest efficacy in phase II human glioblastoma trials, but mechanism relevance of abscopal effect during this response remain unknown. Methods We...
Background Targeted and effective treatment options are needed for solid tumors, including glioblastoma (GBM), where survival rates with standard treatments typically less than 2 years from diagnosis. Solid tumors pose many barriers to immunotherapies, therapy half-life persistence, tumor penetrance, targeting. Therapeutics delivered systemically may not traffic the site. If cellular therapies or drugs able access site, can be directly within tumor, persist duration necessary reduce...
Adult brain tumors establish an immunosuppressive tumor microenvironment as a modality of immune escape, with several immunotherapies designed to overcome this barrier. However, the relationship between cells and in pediatric patients is not well-defined. In study, we sought determine whether model escape observed adult reflected by evaluating NKG2D ligand expression on tissue microarrays created from variety childhood diagnoses, infiltration Natural Killer myeloid cells. We noted disparity...
ABSTRACT Efforts to reduce immunosuppression in the solid tumor microenvironment by blocking recruitment or polarization of associated macrophages (TAM), myeloid derived suppressor cells (MDSCs), have gained momentum recent years. Expanding our knowledge immune cell types, cytokines, factors that are with high-grade disease, both within and circulation, is critical identifying novel targets for immunotherapy. Furthermore, a better understanding how therapeutic regimens, such as Dexamethasone...
ABSTRACT Engineered long lived plasma cells have the potential to be a new area of cell therapy. A key step in developing this therapy is testing model with an intact immune system similar humans. To that end, we developed methods purify, expand, and differentiate non-human primate (NHP; rhesus macaque ) B ex vivo . By comparing several media types conditions, consistently achieved 10-fold expansion NHP using readily available commercial supplement. After only seven days culture, large...
A key step in developing engineered B cells for therapeutic purposes is evaluation immunocompetent, large-animal models. Therefore, we developed methods to purify, expand, and differentiate non-human primate (NHP; rhesus macaque) cells. After 7 days culture, expanded 10-fold, differentiated into a plasma cell phenotype (CD38, CD138), secreted immunoglobulin G. Using single-cell sequencing flow cytometry, verified the presence of genes NHP unearthed less-recognized markers, such as CD59...
Abstract Engineered long lived plasma cells have the potential to be a new area of cell therapy. A key step in developing this therapy is testing model with an intact immune system similar humans. To that end, we developed methods purify, expand, and differentiate non-human primate (NHP; rhesus macaque ) B ex vivo . We consistently achieved 10-fold expansion NHP using readily available commercial supplement. After only seven days culture, large percentages cultures were differentiated. These...
Abstract Engineered immune cells are an exciting therapeutic modality, which survey and attack tumors. Backpacking strategies exploit cell targeting capabilities for delivery of drugs to combat tumors their immune‐suppressive environments. Here, a new platform arming therapeutics through dual receptor polymeric prodrug engineering is developed. Macrophage T engineered express bioorthogonal single chain variable fragment receptor. The binds fluorescein ligand that directs loading with...
Immunotherapy approaches for glioblastoma multiforme have been thus far largely unsuccessful, suggesting unappreciated complexity in glioma biology and immunology. The intra-tumoral heterogeneity of these intrinsic brain tumors results therapies killing only a subset the tumor cells; therefore, therapeutic success will require achieving optimizing an “abscopal effect” where cells not specifically targeted are recognized attacked as bystanders by immune system. We modified immune-competent,...
Abstract Background Interleukin-10 (IL-10) is an immunosuppressive cytokine that inhibits innate and adaptive antitumor immune responses in the tumor microenvironment (TME). Antibody neutralization of IL-10 organotypic slice cultures (TSC) colorectal cancer liver metastases (CRCLM) leads to cell death through. To target blockade TME, we genetically engineered macrophages (GEM) produce neutralizing antibody which hypothesized would reactivate infiltrating cells increase TSC. Methods We...
Ene, Chibawanye I MD; Brempelis, Katherine; Cowan, Courtney; Kreuser, Shannon; Chinn, Harrison; Holland, Eric C MD, PhD; Crane, Courtney Author Information
Abstract Cell-based immunotherapies for cancer, such as chimeric antigen receptor (CAR) T-cells, are effective against certain hematologic malignancies, but less reliably overcome the immunosuppressive tumor microenvironment (TME) of solid tumors to effectively cause cancer remission. Preclinical studies testing interleukin-12 (IL-12), an immune stimulating cytokine that activates T-cells and NK cells, anti-tumor agent have been promising. However, clinical trials demonstrated IL-12 is toxic...
Abstract Introduction Macrophages and monocytes traffic to infiltrate complex solid tumor microenvironments where conditions can promote an immunosuppressive phenotype in resident tumor-associated macrophages that hinder effective anti-tumor immune responses. Ongoing advances cell engineering are being adapted modify into efficacious therapies. However, a limiting factor this promising therapy has been numbers, since obtained from adult peripheral blood mononuclear cells do not expand ex...
Abstract Although it can promote effector T cell function, the summative effect of interleukin-10 (IL-10) in tumor microenvironment (TME) appears to be suppressive; therefore, blocking this critical regulatory cytokine has therapeutic potential enhance antitumor immune function. As macrophages efficiently localize TME, we hypothesized that they could used as a delivery vehicle for drugs designed block pathway. To test our hypothesis, created and evaluated genetically engineered (GEMs)...