A5072225698- Immune Cell Function and Interaction
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Prostate Cancer Treatment and Research
- Heart Failure Treatment and Management
- Advanced biosensing and bioanalysis techniques
- Cardiovascular Function and Risk Factors
- Cancer Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- CRISPR and Genetic Engineering
- Glycosylation and Glycoproteins Research
- Nanoparticle-Based Drug Delivery
- Synthesis and Biological Evaluation
- Health Systems, Economic Evaluations, Quality of Life
University of Minnesota
2020-2024
Twin Cities Orthopedics
2024
University of Minnesota Medical Center
2022
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...
<div>Abstract<p>NK cell tumor infiltration is associated with good prognosis in patients metastatic castration-resistant prostate cancer (mCRPC). NK cells recognize and kill targets by a process called natural cytotoxicity. We hypothesized that promoting an antigen-specific synapse coactivation may enhance function mCRPC. describe tri-specific killer engager (TriKE) construct engages the activating receptor CD16 on prostate-specific membrane antigen (PSMA) mCRPC has IL15 moiety...
<p>MDSC phenotype and suppression.</p>
<p>Patient characteristics.</p>
<p>Calculations of equifunctional dose IL15 compared to PSMA TriKE.</p>
<p>In vivo study results.</p>
<p>Reagent list for time-of-flight mass cytometry (CyTOF).</p>
<p>Antigen specificity test of PSMA TriKE.</p>
<p>Secretome analysis of supernatant from co-culture NK cells with monocytes or MDSCs.</p>
<p>PSMA TriKE testing against patient-derived xenograft (PDX).</p>
<p>PSMA abundance on C4-2 WT and PSMA KO.</p>
<p>CyTOF analysis of NK cell surface expression.</p>
<p>Healthy donors and prostate cancer patient-derived NK cell killing capacity.</p>
<p>Representative images (10X magnification) from the IncuCyte live cell imaging assay.</p>
Limited oxygen (hypoxia) in solid tumors poses a challenge to successful immunotherapy with natural killer (NK) cells. NK cells have impaired cytotoxicity when cultured hypoxia (1% oxygen) but not physiologic (>5%) or atmospheric (20%). We found that changes were regulated at the transcriptional level and accompanied by metabolic dysregulation. Dosing interleukin-15 (IL-15) enhanced cell hypoxia, preactivation feeder bearing IL-21 4-1BBL was even better. Preactivation resulted less...
155 Background: Recombinant human (rh) IL-15, the homeostatic factor for natural killer (NK) cells, is being clinically developed, but it has little antitumor activity alone. B7H3 (CD276) an immune checkpoint inhibitor that associated with poorer prognosis and highly-expressed on prostate cancer. NK cells can be given as allogeneic products and, unlike T do not induce cytokine-release syndrome or neurotoxicity. Here we developed a targeting Tri-Specific Killer Engager (TriKE) novel dual...
NK cells can mediate tumor cell killing by natural cytotoxicity and antibody-dependent cell-mediated (ADCC), an anti-tumor mechanism mediated through the IgG Fc receptor CD16A (FcγRIIIA). polymorphisms conferring increased affinity for positively correlate with clinical outcomes during monoclonal antibody therapy lymphoma, linking binding therapeutic potential via ADCC. We have previously reported on FcγR fusion CD64/16A consisting of extracellular region CD64 (FcγRI), a high-affinity...
Abstract NK cell tumor infiltration is associated with good prognosis in patients metastatic castration-resistant prostate cancer (mCRPC). cells recognize and kill targets by a process called natural cytotoxicity. We hypothesized that promoting an antigen-specific synapse coactivation may enhance function mCRPC. describe tri-specific killer engager (TriKE) construct engages the activating receptor CD16 on prostate-specific membrane antigen (PSMA) mCRPC has IL15 moiety essential for survival,...
Abstract With an annual incidence rate exceeding 660,000 cases, and a death toll surpassing 325,000 per year, head neck cancer (HNC) ranks as the seventh most common in world. Surgery, radiation chemotherapy are used to treat HNC patients with modest variable clinical success. However, these treatments prove less effective for human papillomavirus negative (HPV-) patients, subset of markedly worse prognosis. While significant advancements have been made immunotherapy over past decade, its...
<h3>Background</h3> Shedding of CD16, a potent activating receptor on natural killer (NK) cells that mediates antibody dependent cellular cytotoxicity (ADCC), limits the efficacy NK cell immunotherapies depend this mechanism. Blocking A Disintegrin And Metalloprotease 17 (ADAM17), enzyme clips CD16 upon activation, may overcome limitation. To achieve this, we improved previously described Tri-specific Killer Engager (TriKE) platform. The original TriKE, which showed strong preclinical...