Mecit Kaplan
A5075872357- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Lymphoma Diagnosis and Treatment
- Hematopoietic Stem Cell Transplantation
- Chronic Lymphocytic Leukemia Research
- Immunotherapy and Immune Responses
- Acute Lymphoblastic Leukemia research
- Immune cells in cancer
- Cytomegalovirus and herpesvirus research
- Chronic Myeloid Leukemia Treatments
- Acute Myeloid Leukemia Research
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Platelet Disorders and Treatments
- Single-cell and spatial transcriptomics
- Photosynthetic Processes and Mechanisms
- RNA Interference and Gene Delivery
- Cytokine Signaling Pathways and Interactions
- Carcinogens and Genotoxicity Assessment
- Microbial Metabolic Engineering and Bioproduction
- Phagocytosis and Immune Regulation
- MicroRNA in disease regulation
The University of Texas MD Anderson Cancer Center
2017-2025
University of Arkansas at Little Rock
2015
University of Wisconsin–Madison
1995
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...
Abstract T-cell acute lymphoblastic leukemia (T-ALL) is commonly driven by activating mutations in NOTCH1 that facilitate glutamine oxidation. Here we identify oxidative phosphorylation (OxPhos) as a critical pathway for cell survival and demonstrate direct relationship between , elevated OxPhos gene expression, acquired chemoresistance pre-leukemic leukemic models. Disrupting with IACS-010759, an inhibitor of mitochondrial complex I, causes potent growth inhibition through induction...
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...
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...
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...
Abstract Chimeric antigen receptor (CAR) natural killer (NK) cell immunotherapy offers a promising approach against cancer. However, the molecular mechanisms governing CAR NK activity remain poorly understood. In this study, we identified transcription factor cAMP response element modulator (CREM) as pivotal regulator of function. Using Raji model, single-cell RNA sequencing revealed marked upregulation CREM in cells during peak anti-tumor after adoptive transfer. expression correlated with...
To determine whether gamma delta T cells are essential for the resolution of acute Plasmodium chabaudi adami (P. c. adami) malaria, we depleted from C57BL/6 mice with hamster monoclonal anti-TCR Ab treatment. During period in which control that had received normal IgG completely resolved infections, cell-depleted were unable to suppress their infections. Because number splenic CD4+ alpha beta these anti-TCR-gamma delta-treated nonresolving malaria was similar mice, it appears alone cannot...
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
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...
Abstract Pts with R/R CD30+ lymphoma have few effective therapies available. We previously developed a promising therapy using CB-derived NK that were first IL-12/IL-15/IL-18-preactivated followed by expansion (P+E) K562 feeder cells ex vivo and subsequently complexed ICE® AFM13 (a first-in-class CD30/CD16A bispecific antibody construct) prior to infusion. These cytokine-induced memory-like showed greater in antitumor activity than either P+E or alone. This single-center phase I-II trial...
Wood sugars such as xylose can be used an inexpensive carbon source for biotechnological applications. The model cyanobacterium Synechocystis sp. PCC 6803 lacks the ability to catabolize wood energy source. Here, we generated four strains that heterologously expressed XylAB enzymes, which mediate catabolism, either in combination with or without one of three transporters, namely XylE, GalP, Glf. Except glf, is derived from bacterium Zymomonas mobilis ZM4, heterologous genes were sourced...