A5011430525- CAR-T cell therapy research
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Pluripotent Stem Cells Research
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Multiple Myeloma Research and Treatments
- Cancer Research and Treatments
- Cytomegalovirus and herpesvirus research
- Glycosylation and Glycoproteins Research
- Glioma Diagnosis and Treatment
- Nanowire Synthesis and Applications
- Immune cells in cancer
- Biosimilars and Bioanalytical Methods
- Nanoparticle-Based Drug Delivery
- Virus-based gene therapy research
- Single-cell and spatial transcriptomics
- Acute Myeloid Leukemia Research
- Cancer Immunotherapy and Biomarkers
- Animal Genetics and Reproduction
- Protein Degradation and Inhibitors
- Viral gastroenteritis research and epidemiology
Fate Therapeutics (United States)
2016-2024
GTx (United States)
2024
Sanford Burnham Prebys Medical Discovery Institute
2013-2017
Discovery Institute
2017
R&D Systems (United States)
2014
University of Colorado Denver
2007-2012
National Jewish Health
2012
University of Colorado Health
2007
Denver Health Medical Center
2007
Antibody-dependent cellular cytotoxicity (ADCC) is a key effector mechanism of natural killer (NK) cells that mediated by therapeutic monoclonal antibodies (mAbs). This process facilitated the Fc receptor CD16a on human NK cells. appears to be only activating cleaved metalloprotease disintegrin and metalloproteinase-17 upon stimulation. We previously demonstrated point mutation prevents this activation-induced surface cleavage. noncleavable variant now further modified include high-affinity...
The development of immunotherapeutic monoclonal antibodies targeting checkpoint inhibitory receptors, such as programmed cell death 1 (PD-1), or their ligands, PD-L1, has transformed the oncology landscape. However, durable tumor regression is limited to a minority patients. Therefore, combining immunotherapies with those receptors promising strategy bolster antitumor responses and improve response rates. Natural killer (NK) cells have potential augment inhibition therapies, PD-L1/PD-1...
Maturation of human natural killer (NK) cells as defined by accumulation cell-surface expression CD57 is associated with increased cytotoxic character and TNF IFNγ production upon target-cell recognition. Notably, multiple studies point to a unique role for CD57+ NK in cancer immunosurveillance, yet there scant information about how they mature. In this study, we show that pharmacologic inhibition GSK3 kinase peripheral blood expanded ex vivo IL15 greatly enhances upregulation late-stage...
Abstract Allogeneic natural killer (NK) cell adoptive transfer is a promising treatment for several cancers but less effective the of multiple myeloma. In this study, we report on quadruple gene-engineered induced pluripotent stem (iPSC)-derived NK cells designed mass production from renewable source and dual targeting against myeloma through introduction an cell-optimized chimeric antigen receptor (CAR) specific B maturation (BCMA) high affinity, non-cleavable CD16 to augment...
Abstract Lymphocyte activation is regulated by costimulatory and inhibitory receptors, of which both B T lymphocyte attenuator (BTLA) CD160 engage herpesvirus entry mediator (HVEM). Notably, it remains unclear how HVEM functions with each its ligands during immune responses. In this study, we show that specifically activates on effector NK cells challenged virus-infected cells. Human CD56dim were costimulated but not other receptors share the LIGHT, Lymphotoxin-α, or BTLA. enhanced human...
The advent of chimeric antigen receptor (CAR) T cell therapies has transformed the treatment hematological malignancies; however, broader therapeutic success CAR cells been limited in solid tumors because their frequently heterogeneous composition. Stress proteins MICA and MICB (MICA/B) family are broadly expressed by tumor following DNA damage but rapidly shed to evade immune detection.
Natural killer (NK) cells mediate the cytolysis of transformed and are currently used as an adoptive cellular therapy to treat cancer. Infection with human cytomegalovirus has been shown expand a subset "adaptive" NK expressing activation receptor NKG2C that have preferred functional attributes distinct from conventional cells. Because delivers strong activating signal cells, we hypothesized could specifically trigger NK-cell-mediated antitumor responses. To elicit tumor-directed response...
Background Antibody therapies can direct natural killer (NK) cells to tumor cells, tumor-associated and suppressive immune mediate antibody-dependent cell-mediated cytotoxicity (ADCC). This antigen-specific effector function of human NK is mediated by the IgG Fc receptor CD16A (FcγRIIIA). Preclinical clinical studies indicate that increasing binding affinity avidity for antibodies improves therapeutic potential ADCC. CD64 (FcγRI), expressed myeloid but not only high uniquely capable stably...
Abstract Both peptidoglycan and muropeptides potently modulate inflammatory innate immune responses. The secreted Listeria monocytogenes p60 autolysin digests promotes bacterial infection in vivo. Here, we report that contributes to subversion of NK cell activation IFN-γ production. L. deficient for (Δp60) competed well expansion mice doubly IFNAR1 IFN-γR1 or singly IFN-γR1, but not wild-type, IFNAR1−/−, TLR2−/− mice. restored competitiveness p60-deficient bacteria suggested a specific role...
The T cell response to B lymphomas differs from the majority of solid tumors in that malignant cells themselves are derived lymphocytes, key players immune response. therefore well situated manipulate their surrounding microenvironment enhance tumor growth and minimize anti-tumor responses. We analyzed effect on a transplantable lymphoma found iNKT suppressed CD8+ Lymphoma transplanted into syngeneic wild type (WT) mice or Jalpha18−/− specifically lack grew initially at same rate, but only...
Abstract Immune cell therapy has proven highly effective for the treatment of multiple myeloma (MM). However, key challenges remain that include disease relapse, limited patient access, and inability to effectively combine with existing standard-of-care therapies. Rapid progress in development off-the-shelf, multiplexed-engineered, induced pluripotent stem (iPSC)-derived therapies enables large-scale manufacture immune cells incorporating novel synthetic controls function improve fitness,...
Abstract Introduction: B7-H3 (CD276) has gained significant clinical interest as a pan-tumor target antigen for development of various immuno-oncology agents. Due to its broad expression on wide variety solid tumors and minimal normal tissues, is an ideal tumor target. Additionally, high levels are found “immunologically cold” such glioblastoma multiforme, prostate cancer, head neck cancer soft tissue sarcomas, which typically have poor response approved immune therapies. To effectively with...
Abstract Natural killer (NK) cells are potent antitumor effectors that play an important role in innate and adaptive immunity. Despite recent clinical advances the therapeutic use of NK cells, significant opportunities remain to harness their full potential adoptive immunotherapy. For example, achieving consistent manufacturing cancer immunotherapies using patient- donor-sourced remains a challenge delivering therapies all patients who may benefit. There is also need improve efficacy...
Abstract The development of PD1/PDL1 targeting checkpoint inhibitors (CI) has transformed the oncology landscape, providing long term remissions in multiple indications. However, many tumor subtypes are resistant to blockade therapy, and relapse remains a significant concern. Novel therapeutic approaches with ability overcome CI resistance needed, there is opportunity for therapies capable additively or synergistically enhancing T-cell activation recruitment when combined CI. Adoptive...