A5086415382- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cancer Research and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Nanowire Synthesis and Applications
- Virus-based gene therapy research
- Monoclonal and Polyclonal Antibodies Research
- Renal and related cancers
- Biosimilars and Bioanalytical Methods
- Hematopoietic Stem Cell Transplantation
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Chronic Lymphocytic Leukemia Research
- Cell Adhesion Molecules Research
- 3D Printing in Biomedical Research
- CRISPR and Genetic Engineering
- S100 Proteins and Annexins
- RNA Research and Splicing
- Chemokine receptors and signaling
- Advanced biosensing and bioanalysis techniques
- Chromatography in Natural Products
- Cutaneous lymphoproliferative disorders research
Baylor College of Medicine
2016-2025
Texas Children's Hospital
2014-2024
Houston Methodist
2014-2024
Methodist Hospital
2014-2024
Data Harbor (United States)
2015
Niigata University of Pharmacy and Medical and Life Sciences
2013-2014
Niigata University
2004-2014
RMIT University
2008-2012
Japan Society for the Promotion of Science
2010-2011
The University of Tokyo
2011
The adoptive transfer of T cells redirected to tumor-associated antigens via transgenic expression chimeric antigen receptors (CARs) has produced tumor responses, even in patients with refractory diseases. To target pancreatic cancer, we generated CAR directed against prostate stem cell (PSCA) and demonstrated specific lysis. However, tumors employ immune evasion strategies such as the production inhibitory cytokines, which limit persistence function. Thus, protect our from immunosuppressive...
Chimeric antigen receptor-modified T cells (CAR cells) produce proinflammatory cytokines that increase expression of T-cell checkpoint signals such as PD-L1, which may inhibit their functionality against solid tumors. In this study, we evaluated in human tumor xenograft models the properties an oncolytic adenovirus (Onc.Ad) with a helper-dependent Ad (HDAd) expresses PD-L1 blocking mini-antibody (mini-body; HDPDL1) strategy to enhance CAR killing. Coadministration these agents (CAd-VECPDL1)...
In solid tumors, chimeric antigen receptor (CAR)-modified T cells must overcome the challenges of immunosuppressive tumor microenvironment. We hypothesized that pre-treating tumors with our binary oncolytic adenovirus (CAd), which produces local oncolysis and expresses immunostimulatory molecules, would enhance antitumor activity HER2-specific CAR cells, alone are insufficient to cure tumors. tested multiple cytokines in conjunction PD-L1-blocking antibody found Ad-derived IL-12p70 prevents...
The adoptive transfer of genetically engineered T cells expressing chimeric antigen receptors (CARs) has emerged as a transformative cancer therapy with curative potential, precipitating wave preclinical and clinical studies in academic centers the private sector. Indeed, significant effort been devoted to improving benefit by incorporating accessory genes/CAR endodomains designed enhance cellular migration, promote vivo expansion/persistence or safety genetic programming enable recognition...
The success of adoptively transferred tumor-directed T cells requires them to survive and expand in vivo. Most tumors, however, employ immune evasion mechanisms, including the production inhibitory cytokines that limit vivo T-cell persistence effector function. To protect from such negative influences, we generated a chimeric cytokine receptor which interleukin (IL) 4 exodomain was fused IL7 endodomain. We thereby inverted effects tumor-derived IL4 so proliferation activation tumor directed...
The adoptive transfer of chimeric antigen receptor (CAR)-modified T cells has produced tumor responses even in patients with refractory diseases. However, the paucity antigens that are selective resulted, on occasion, "on-target, off-tumor" toxicities. To address this issue, we developed an approach to render responsive expression pattern present exclusively at by using a trio novel receptors. Using pancreatic cancer as model, demonstrate how engineered receptors recognize prostate stem cell...
The adoptive transfer of T cells redirected to tumor via chimeric antigen receptors (CARs) has produced clinical benefits for the treatment hematologic diseases. To extend this approach breast cancer, we generated CAR directed against mucin1 (MUC1), an aberrantly glycosylated neoantigen that is overexpressed by malignant and whose expression been correlated with poor prognosis. Furthermore, protect our tumor-targeted from elevated levels immune-inhibitory cytokines present in milieu,...
Background Successful targeting of solid tumors such as breast cancer (BC) using chimeric antigen receptor (CAR) T cells has proven challenging, largely attributed to the immunosuppressive tumor microenvironment (TME). Myeloid-derived suppressor (MDSCs) inhibit CAR cell function and persistence within TME. To overcome this challenge, we have developed tumor-associated mucin 1 (MUC1) with a novel costimulatory that targets necrosis factor–related apoptosis-inducing ligand 2 (TR2) expressed on...
Chimeric antigen receptor (CAR)-mediated targeting of T lineage antigens for the therapy blood malignancies is frequently complicated by self-targeting CAR cells or their excessive differentiation driven constant signaling. Expression CARs CD7, a pan-T cell highly expressed in and some myeloid leukemias, produces robust fratricide often requires additional mitigation strategies, such as CD7 gene editing. In this study, we show can be fully prevented using ibrutinib dasatinib, pharmacologic...
Cell therapies for solid tumors are thwarted by the hostile tumor microenvironment (TME) and heterogeneous expression of target antigens. We address both limitations with a novel class chimeric antigen receptors based on plant lectins, which recognize aberrant sugar residues that 'hallmark' malignant associated stromal cells. have expressed in T cells modified lectin from banana, H84T BanLec, attached to receptor (H84T-CAR) recognizes high-mannose (asparagine residue five nine mannoses)....
Background B7 homolog 3 (B7-H3), an overexpressed antigen across multiple solid cancers, represents a promising target for CAR T cell therapy. This study investigated the expression of B7-H3 various tumors and developed novel monoclonal antibodies (mAbs) targeting Methods Expression was evaluated using RNA-seq data from TCGA, TARGET, GTEx datasets by flow cytometry staining. B7-H3-specific mAbs were immunizing mice with human B7-H3, screening ELISA, analyzing kinetics surface plasmon...
Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease caused by selective loss of motor neurons. In the ALS neurons, TAR DNA-binding protein 43 kDa (TDP-43) dislocated from nucleus to cytoplasm and forms inclusions, suggesting that a nuclear function TDP-43 may underlie pathogenesis ALS. functions in RNA metabolism include regulation transcription, mRNA stability, alternative splicing pre-mRNA. However, tissue affected with has not been elucidated. We sought...
Background C-type lectin-like molecule 1 (CLL-1) is highly expressed in acute myeloid leukemia (AML) but absent primitive hematopoietic progenitors, making it an attractive target for a chimeric antigen receptor (CAR) T-cell therapy. Here, we optimized our CLL-1 CAR anti-leukemic activity mouse xenograft models of aggressive AML. Methods First, the using different spacer, transmembrane and costimulatory sequences. We used second retroviral vector to coexpress transgenic IL15. measured...
Abstract Coincubation of neutrophils with TNF inhibited the chemoattractant-directed migration under agarose and enhanced their in multiwell chemotaxis chamber. To assess physiological significance these differing vitro effects, ex vivo investigations were performed using animal models. Neutrophils from peripheral blood rabbits preadministered systemic showed impaired ability to migrate toward chemoattractants vitro. In addition, administration suppressed zymosan-activated plasma-induced...
<h3>Background</h3> Pre-clinical and clinical studies have shown that the infusion of CAR T cells with a naive-like (T<sub>N</sub>) central memory (T<sub>CM</sub>) phenotype is associated prolonged in vivo cell persistence superior anti-tumor effects. To optimize maintenance such populations during vitro preparation process, we explored impact exposure to both traditional [fetal bovine serum (FBS), human AB (ABS)] non-traditional [human platelet lysate (HPL) - xeno-free protein supplement...
Although tyrosine kinase inhibitors is effective for dramatically reducing CML cells, it might be difficult to eradicate completely the stem cells.We aimed clarify safety and effects of WT1 peptide vaccination in combination with imatinib therapy a patient.A 51 year-old male CP, who showed resistance against 2.5 years, began treated 9mer modified-type peptides standard dose imatinib.Although every 2-week-administration 22 weeks did not show definite on quantification bcr-abl transcripts, by...
Although the roles of each low-frequency immunocompetent cells such as dendritic (DCs), γδT cells, and Treg in induction acute or chronic graft versus host disease (GVHD) have been discussed several reports, there are few papers dealing with an evaluation these together simultaneously patients hematopoietic stem cell transplantation (HSCT) explored kinetics association GVHD.In present study, we assessed number plasmacytoid DCs (pDCs), myeloid (mDCs), serially who received allogeneic HSCT...
Apigenin, a common dietary flavonoid present in many fruits and vegetables, is nonmutagenic chemopreventive agent. In the study, we investigated effect of apigenin on radiosensitivity SQ-5 cells, which are derived from human lung carcinoma. Actively growing cells were incubated for 16 h at 37°C medium containing 40 μM apigenin. The then irradiated with X-rays further 8 h. Radiosensitivity was assessed using clonogenic assay. Apoptosis necrosis acridine orange/ethidium bromide double...