A5090476415- CAR-T cell therapy research
- Reproductive Biology and Fertility
- Sperm and Testicular Function
- Viral Infectious Diseases and Gene Expression in Insects
- Prenatal Screening and Diagnostics
- T-cell and B-cell Immunology
- Reproductive Health and Technologies
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Toxoplasma gondii Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Assisted Reproductive Technology and Twin Pregnancy
- Chronic Lymphocytic Leukemia Research
- Immune Cell Function and Interaction
- Nanowire Synthesis and Applications
Memorial Sloan Kettering Cancer Center
2024
Kettering University
2024
Weill Cornell Medicine
2022
Cornell University
2022
Abstract Background Spermatozoa with the highest motility retain a superior genomic integrity, and elevated sperm chromatin fragmentation (SCF) has been linked to lower ability of conceptus develop implant. Therefore, utilization selection method, such as microfluidic (MFSS), is capable reducing SCF by yielding most motile fraction spermatozoa embryo developmental competence. What remains unclear, however, causal mechanism that links an impaired development. Objectives To identify...
CD33 is a tractable target in acute myeloid leukemia (AML) for chimeric antigen receptor (CAR) T cell therapy, but clinical success lacking. We developed 3P14HLh28Z, novel CD33-directed CD28/CD3Z-based CAR derived from high-affinity binder obtained through membrane-proximal fragment immunization humanized mice. found that exclusively with the domain of necessary identification binders Compared clinically validated lintuzumab-based cells targeting distal epitopes, 3P14HLh28Z showed enhanced...
To assess the role of evaluating sperm chromatin fragmentation (SCF) as a tool to guide treatment in couples who achieved unexpectedly poor clinical outcomes after intracytoplasmic injection (ICSI).
Chimeric antigen receptor (CAR) T-cell therapy has resulted in remarkable clinical success the treatment of B-cell malignancies. However, its efficacy solid tumors is limited, primarily by target heterogeneity. To overcome heterogeneity, we developed CAR T cells that overexpress LIGHT, a ligand both lymphotoxin-β on cancer and herpes virus entry mediator immune cells. LIGHT-expressing displayed antigen-directed cytotoxicity mediated antigen-independent killing through interaction LIGHT with...
<p>(A) ELISA quantification of soluble LIGHT in cell culture media after 24 hours incubation. (B) Supernatant from LIGHT-CAR T cells and second-generation CAR were added to corresponding vitro cytolysis was assessed against AsPC1. Data is representative 2 independent experiments two different donors. (C) MIAPACA2. (D) Cytotoxicity assay with various mesothelin-directed constructs the addition recombinant 3 (E) Mesothelin-directed exhibited similar proliferation a repetitive antigen...
<p>(A) Violin plots showing quality metrics of single cells included in downstream analysis. nCount RNA: number RNA unique molecular identifiers (UMI); nFeature detected genes; nCount_ADT: antibody UMI; nFeature_ADT: antibodies; percent.mt: percentage mitochondrial gene expression; HTO_margin: difference between signals for the hashtag with highest signal and second signal. (B) (C) Weighted-nearest neighbor (WNN) UMAP colored by condition (CAR T cell construct timepoint) (top) CD4+ vs...
<p>(A) Flow cytometric analysis of LTβR expression MIAPACA2 cells after CRISPR knockout (KO). KO were also transduced with non-signaling without intracellular signaling portion (tLTBR). (B) healthy human donor-derived mesothelin-targeted CAR T cocultured tumor expressing GFP and firefly luciferase at different effector to ratios. Bioluminescence was measured 72 hours later plotted as a percentage the signal detected in coculture non-functional Meso-DEL-CAR cells. Plots represent 3...
<p>(A) CAR T cells infiltration and expression of LIGHT at the tumor site was quantified by flow cytometric analysis on day 14 post cell treatment. (B) (C) Quantification per gram AsPC1 mass Plot is representative 4 to 5 mice treatment group. Immunohistochemistry staining mesothelin-negative cancer line, Panc1. Negative control. (D) mesothelin-positive MDA-MB-231. Positive (E) various PDX slides samples validate their mesothelin expression. (F) Flow in PDAC2, one selected for vivo...
<p>(A) Histopathological analysis images of certain organs in the 3 CAR-treated groups following full necropsy on day 30. Representative regions displaying lesion or absence at 20magnification are stained with H&E. Scale bar 100 microns. (B) Histologic examination various and tissues 30 after CAR T cell treatment. (C) Serum chemistry values mice Red represents higher than reference range blue lower range.</p>
<p>(A) Transgene expression of the CAR constructs after retroviral transduction human T cells by flow cytometry. CD19 were used as irrelevant cell control. (B-D) Healthy donor-derived mesothelin-targeted cocultured with tumor expressing GFP and firefly luciferase at different effector to ratios. Bioluminescence was measured 72 hours later plotted a percentage signal detected alone (max bioluminescence signal). Associated mesothelin corresponding mesothelin-positive lines are shown. JMN...
<div>Abstract<p>Chimeric antigen receptor (CAR) T-cell therapy has resulted in remarkable clinical success the treatment of B-cell malignancies. However, its efficacy solid tumors is limited, primarily by target heterogeneity. To overcome heterogeneity, we developed CAR T cells that overexpress LIGHT, a ligand both lymphotoxin-β on cancer and herpes virus entry mediator immune cells. LIGHT-expressing displayed antigen-directed cytotoxicity mediated antigen-independent killing...