Rafet Başar
A5032622792- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Hematopoietic Stem Cell Transplantation
- Immunotherapy and Immune Responses
- Lymphoma Diagnosis and Treatment
- Virus-based gene therapy research
- Chronic Lymphocytic Leukemia Research
- Cytomegalovirus and herpesvirus research
- Single-cell and spatial transcriptomics
- Acute Myeloid Leukemia Research
- Cancer Genomics and Diagnostics
- Immune cells in cancer
- CRISPR and Genetic Engineering
- Immunodeficiency and Autoimmune Disorders
- Gene Regulatory Network Analysis
- SARS-CoV-2 and COVID-19 Research
- RNA modifications and cancer
- RNA Interference and Gene Delivery
- Pluripotent Stem Cells Research
- Phagocytosis and Immune Regulation
- Ferroptosis and cancer prognosis
- Gene expression and cancer classification
- Chronic Myeloid Leukemia Treatments
The University of Texas MD Anderson Cancer Center
2016-2025
Istanbul University
2013-2021
Texas Children's Hospital
2017
Baylor College of Medicine
2017
Creative Commons
2017
Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in B-cell cancers. However, CAR T cells can induce substantial toxic effects, and the manufacture of is complex. Natural killer (NK) that have been modified to express an anti-CD19 potential overcome these limitations.
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...
Abstract There is a pressing need for allogeneic chimeric antigen receptor (CAR)-immune cell therapies that are safe, effective and affordable. We conducted phase 1/2 trial of cord blood-derived natural killer (NK) cells expressing anti-CD19 interleukin-15 (CAR19/IL-15) in 37 patients with CD19 + B malignancies. The primary objectives were safety efficacy, defined as day 30 overall response (OR). Secondary included 100 response, progression-free survival, survival CAR19/IL-15 NK persistence....
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...
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...
T cells engineered with chimeric antigen receptors (CARs) have revolutionized the field of cell therapy and changed paradigm treatment for many patients relapsed or refractory B-cell malignancies. Despite this progress, there are limitations to CAR-T in both autologous allogeneic settings, including practical, logistical, toxicity issues. Given these concerns, is a rapidly growing interest natural killer as alternative vehicles CAR engineering, given their unique biological features...
Integration of single-cell multiomics profiles generated by different technologies from the same biological sample is still challenging. Previous approaches based on shared features have only provided approximate solutions. Here, we present a novel mathematical solution named bi-order canonical correlation analysis (bi-CCA), which extends widely used CCA approach to iteratively align rows and columns between data matrices. Bi-CCA generally applicable combinations any two modalities....
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...
BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients alternative donor transplants, which are being performed increasing numbers. BKV-HC typically results painful hematuria, urinary obstruction, and renal dysfunction, without definitive therapeutic option.We clinical trial (ClinicalTrials.gov identifier: NCT02479698) to assess the feasibility, safety, efficacy administering most...
Sepsis remains a leading cause of death for humans and currently has no pathogenesis-specific therapy. Hampered progress is partly due to lack insight into deep mechanistic processes. In the past decade, deciphering functions small noncoding miRNAs in sepsis pathogenesis became dynamic research topic. To screen new miRNA targets therapeutics, we used samples array analysis PBMCs from patients with control individuals, blood 2 cohorts sepsis, multiple animal models: mouse cecum ligation...
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...