Luis Muniz-Feliciano
A5014526727- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Cytomegalovirus and herpesvirus research
- Lymphoma Diagnosis and Treatment
- Autophagy in Disease and Therapy
- Toxoplasma gondii Research Studies
- SARS-CoV-2 and COVID-19 Research
- Hematopoietic Stem Cell Transplantation
- Virus-based gene therapy research
- Immune cells in cancer
- Immunotherapy and Immune Responses
- COVID-19 Clinical Research Studies
- Cellular transport and secretion
- Viral Infectious Diseases and Gene Expression in Insects
- CRISPR and Genetic Engineering
- Retinal Diseases and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Pluripotent Stem Cells Research
- Mesenchymal stem cell research
- Phagocytosis and Immune Regulation
- Acute Myeloid Leukemia Research
- Heme Oxygenase-1 and Carbon Monoxide
The University of Texas MD Anderson Cancer Center
2019-2025
Case Western Reserve University
2013-2017
University School
2013-2017
Glioblastoma multiforme (GBM), the most aggressive brain cancer, recurs because glioblastoma stem cells (GSCs) are resistant to all standard therapies. We showed that GSCs, but not normal astrocytes, sensitive lysis by healthy allogeneic natural killer (NK) in vitro. Mass cytometry and single-cell RNA sequencing of primary tumor samples revealed GBM tumor-infiltrating NK acquired an altered phenotype associated with impaired lytic function relative matched peripheral blood from patients or...
Natural killer (NK)-cell recognition and function against NK-resistant cancers remain substantial barriers to the broad application of NK-cell immunotherapy. Potential solutions include bispecific engagers that target activity via an NK-activating receptor when simultaneously targeting a tumor-specific antigen, as well enhancing functionality using IL12/15/18 cytokine pre-activation.
Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells is promising, with early-phase clinical studies showing encouraging responses. However, the transcriptional signatures that control fate CAR-NK after infusion and factors influence tumor remain poorly understood. We performed single-cell RNA sequencing mass cytometry to study heterogeneity their in vivo evolution adoptive transfer, from phase relapse. Using a preclinical model noncurative lymphoma samples responder...
Toxoplasma gondii resides in an intracellular compartment (parasitophorous vacuole) that excludes transmembrane molecules required for endosome-lysosome recruitment. Thus, the parasite survives by avoiding lysosomal degradation. However, autophagy can re-route parasitophorous vacuole to lysosomes and cause killing. This raises possibility T. may deploy a strategy prevent autophagic targeting maintain non-fusogenic nature of vacuole. We report activated EGFR endothelial cells, retinal pigment...
Glioblastoma (GBM) is an aggressive brain cancer with limited therapeutic options. Natural killer (NK) cells are innate immune strong anti-tumor activity and may offer a promising treatment strategy for GBM. We compared the anti-GBM of NK engineered to express interleukin (IL)-15 or IL-21. Using multiple in vivo models, IL-21 were superior IL-15 both terms safety long-term activity, locoregionally administered proving toxic ineffective at tumor control. displayed unique chromatin...
Multiple factors in the design of a chimeric antigen receptor (CAR) influence CAR T-cell activity, with costimulatory signals being key component. Yet, impact domains on downstream signaling and subsequent functionality CAR-engineered natural killer (NK) cells remains largely unexplored. Here, we evaluated various CAR-NK cell using CD70-targeting CAR. We found that CD28, molecule not inherently present mature NK cells, significantly enhanced antitumor efficacy long-term cytotoxicity both...
Macroautophagy/autophagy is an intracellular stress survival and recycling system whereas phagocytosis internalizes material from the extracellular milieu; yet, both pathways utilize lysosomes for cargo degradation. Whereas autophagy occurs in all cells, performed by cell types such as macrophages retinal pigment epithelial (RPE) cells of eye where it supported noncanonical process termed LC3-associated (LAP). Autophagy LAP are distinct that use many same mediators must compete cellular...
Toxoplasma gondii infects both hematopoietic and nonhematopoietic cells can cause cerebral ocular toxoplasmosis, as a result of either congenital or postnatally acquired infections. Host protection likely acts at cellular levels to control the parasite. CD40 is key factor for against toxoplasmosis. We determined if induces anti-T. activity level cells. Engagement on various endothelial including human microvascular brain cells, umbilical vein mouse cell line well retinal pigment epithelial...
Targeting of Toxoplasma gondii by autophagy is an effective mechanism which host cells kill the protozoan. Thus, parasite must avoid autophagic targeting to survive. Here we show that mammalian cytoplasmic molecule Focal Adhesion Kinase (FAK) becomes activated during invasion cells. Activated FAK appears accompany formation moving junction (as assessed expression protein RON4). activation was inhibited approaches impaired β1 and β3 integrin signaling. caused Src in turn mediated Epidermal...
Natural killer (NK) cells are innate lymphocytes recognized for their important role against tumor cells. NK expressing chimeric antigen receptors (CARs) have enhanced effector function various type of cancer and attractive contenders the next generation immunotherapies. However, a number factors hindered application cellular therapy, including poor in vitro growth kinetics relatively low starting percentages within mononuclear cell fraction peripheral blood or cord (CB). To overcome these...
CD226 plays a vital role in natural killer (NK) cell cytotoxicity, interacting with its ligands CD112 and CD155 to initiate immune synapse formation, primarily through leukocyte function-associated-1 (LFA-1). Our study examined the of NK surveillance acute myeloid leukemia (AML). cells patients AML had lower expression CD226. CRISPR-Cas9 deletion led reduced LFA-1 recruitment, poor decreased anti-leukemic activity. Engineering express chimeric antigen receptor targeting CD38 (CAR38) could...
Key Points Cytomegalovirus reactivation and interleukin 15 are major contributors to NK cell repertoire diversity maturation after CBT. An immature subset characterized by low index poor effector function was highly predictive of relapse
Adoptive cell therapy with virus-specific T cells has been used successfully to treat life-threatening viral infections, supporting application of this approach coronavirus disease 2019 (COVID-19). We expand severe acute respiratory syndrome 2 (SARS-CoV-2) from the peripheral blood COVID-19-recovered donors and non-exposed controls using different culture conditions. observe that choice cytokines modulates expansion, phenotype, hierarchy antigenic recognition by SARS-CoV-2 cells. Culture...
Abstract Virus-specific T cells have proven highly effective for the treatment of severe and drug-refractory infections after hematopoietic stem cell transplant (HSCT). However, efficacy these is hindered by use glucocorticoids, often given to patients management complications such as graft-versus-host disease. To address this limitation, we developed a novel strategy rapid generation good manufacturing practice (GMP)–grade glucocorticoid-resistant multivirus-specific (VSTs) using clustered...
Myelodysplastic syndrome and acute myeloid leukemia (AML) belong to a continuous disease spectrum of malignancies with poor prognosis in the relapsed/refractory setting necessitating novel therapies. Natural killer (NK) cells from patients display global dysfunction impaired killing capacity, altered metabolism, an exhausted phenotype at single-cell transcriptomic proteomic levels. In this study, we identified that was mediated through cross-talk between NK blasts cell-cell contact. cell...
Acute graft-vs.-host (GVHD) disease remains a common complication of allogeneic stem cell transplantation with very poor outcomes once the becomes steroid refractory. Mesenchymal cells (MSCs) represent promising therapeutic approach for treatment GVHD, but so far this strategy has had equivocal clinical efficacy. Therapies using MSCs require optimization taking advantage plasticity these in response to different microenvironments. In study, we aimed optimize cord blood tissue derived (CBti...
Background B cells play a pivotal role in regulating the immune response. The induction of cell-mediated immunosuppressive function requires cell activating signals. However, mechanisms by which activated mediate T-cell suppression are not fully understood. Methods We investigated potential contribution metabolic activity to performing vitro experiments and analyzing clinical samples using mass cytometry single-cell RNA sequencing. Results Here we show that following activation, acquire an...
ABSTRACT Glioblastoma, the most aggressive brain cancer, often recurs because glioblastoma stem cells (GSCs) are resistant to all standard therapies. Here, we show that patient-derived GSCs, but not normal astrocytes, highly sensitive lysis by healthy allogeneic natural killer (NK) in vitro . In contrast, single cell analysis of autologous, tissue infiltrating NK isolated from surgical samples high-grade patient tumors using mass cytometry and RNA sequencing revealed an abnormal phenotype...
<div>Abstract<p>Multiple factors in the design of a chimeric antigen receptor (CAR) influence CAR T-cell activity, with costimulatory signals being key component. Yet, impact domains on downstream signaling and subsequent functionality CAR-engineered natural killer (NK) cells remains largely unexplored. Here, we evaluated various CAR-NK cell using CD70-targeting CAR. We found that CD28, molecule not inherently present mature NK cells, significantly enhanced antitumor efficacy...
<p>In vitro characterization of the CAR27 constructs.</p>
<p>CAR27-28ζ NK cells show polyfunctionality.</p>
<p>Expression of CD70 at the protein and mRNA levels in different tumor types.</p>