A5075328927- Virus-based gene therapy research
- CAR-T cell therapy research
- Herpesvirus Infections and Treatments
- Cancer Research and Treatments
- Neuroblastoma Research and Treatments
- Chronic Myeloid Leukemia Treatments
- Ovarian cancer diagnosis and treatment
- Immunotherapy and Immune Responses
- Acute Lymphoblastic Leukemia research
- RNA Interference and Gene Delivery
- Sarcoma Diagnosis and Treatment
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- Acute Myeloid Leukemia Research
- Mast cells and histamine
- Protein Degradation and Inhibitors
- Mechanisms of cancer metastasis
- RNA modifications and cancer
- interferon and immune responses
- Food Allergy and Anaphylaxis Research
- Monoclonal and Polyclonal Antibodies Research
- Sarcoidosis and Beryllium Toxicity Research
- IL-33, ST2, and ILC Pathways
- Neurofibromatosis and Schwannoma Cases
- Immunodeficiency and Autoimmune Disorders
Nationwide Children's Hospital
2014-2024
Kaohsiung Medical University
2023
Kaohsiung Medical University Chung-Ho Memorial Hospital
2023
Chi Mei Medical Center
2023
National Yunlin University of Science and Technology
2021
The Ohio State University
2014-2018
Cincinnati Children's Hospital Medical Center
2009-2015
University of Rochester
2005-2008
University of Rochester Medical Center
2007
Oncolytic virotherapy is an effective immunotherapeutic approach for cancer treatment via a multistep process including direct tumor cell lysis, induction of cytotoxic or apoptosis-sensitizing cytokines and promotion antitumor T responses. Solid tumors limit the effectiveness immunotherapeutics in diverse ways such as secretion immunosuppressive expression immune inhibitory ligands to inhibit function. Blocking programmed death protein (PD)-1 signaling, which mediates suppression engagement...
Oncolytic viral (OV) therapy, which uses genetically engineered tumor-targeting viruses, is being increasingly used in cancer clinical trials due to the direct cytolytic effects of this treatment that appear provoke a robust immune response against tumor. As OVs enter tumor cells, intrinsic host defenses have potential hinder replication and spread within mass. In report, we show histone deacetylase 6 (HDAC6) cells appears alter trafficking post-entry from nucleus toward lysosomes. glioma...
Ewing sarcoma is a highly aggressive cancer that promotes the infiltration and activation of pro-tumor M2-like macrophages. Oncolytic virotherapy selectively infects destroys cells promising option for treating sarcoma. The effect tumor macrophages on oncolytic virus therapy, however, variable among solid tumors unknown in We tested effects macrophage reduction using liposomal clodronate (Clodrosome) trabectedin antitumor efficacy intratumoral herpes simplex virus, rRp450, two xenograft...
Multiple studies have indicated that in addition to direct oncolysis, virotherapy promotes an antitumor cytotoxic T cell response important for efficacy. To study this phenomenon further, we tested three syngeneic murine sarcoma models displayed varied degrees of permissiveness oncolytic herpes simplex virus replication and cytotoxicity vitro, with the most permissive being comparable some human tumor lines. The vivo effect ranged from no or modest complete regression protection rechallenge....
Oncolytic viruses are an emerging class of cancer therapeutics that couple cytotoxicity with the induction anti-tumor immune response. Host-virus interactions complex and modulated by a tumor microenvironment whose immunosuppressive activities can limit effectiveness immunotherapies. In effort to improve this aspect oncolytic virotherapy, we combined herpes virus HSV1716 transforming growth factor beta receptor 1 (TGF-βR1) inhibitor A8301 treat syngeneic models murine rhabdomyosarcoma. Mice...
GP101 is a single chain diabody composed of Fv regions antibodies directed to CD3 and CD19. It designed mimic commercial blinatumomab (Blincyto®) that simultaneously co-engages patient T lymphocytes CD19 positive B cell leukemias lymphomas, facilitating their targeted destruction. This study details the purification protein development highly sensitive ELISA for its detection, achieving sensitivity 15pg/mL in 25% mouse serum. has been validated according GLP standards.
Abstract Purpose: Novel therapeutic regimens are needed to improve dismal outcomes associated with late-stage ovarian cancer. Oncolytic viruses currently being tested in patients Here, we the efficacy of combining doxorubicin 34.5ENVE, an oncolytic herpes simplex virus transcriptionally driven by a modified stem cell–specific nestin promoter, and encoding for antiangiogenic Vasculostatin-120 (VStat120) use against progressive Experimental Design: Antitumor 34.5ENVE was assessed cancer cell...
// Mark A. Currier 1 , Les Sprague Tilat Rizvi 2 Brooke Nartker Chun-Yu Chen Pin-Yi Wang Brian J. Hutzen Meghan R. Franczek Ami V. Patel Katherine E. Chaney Keri Streby 1,3 Jeffrey Ecsedy 4 Joe Conner 5 Nancy Ratner and Timothy P. Cripe Center for Childhood Cancer Blood Diseases, Nationwide Children’s Hospital, The Ohio State University, Columbus, Ohio, USA Division of Experimental Hematology Biology, Cincinnati Hospital Medical Center; Cincinnati, 3 Hematology/Oncology/Blood Marrow...
T cells redirected to cancer either via a chimeric antigen receptor (CAR-T) or bispecific molecule have been breakthrough technologies; however, CAR-T require individualized manufacturing and bispecifics generally continuous infusions. We created an off-the-shelf, single-dose solution for achieving prolonged systemic serum levels of protein immunotherapeutics adeno-associated virus (AAV) gene transfer. demonstrate proof principle in CD19 + lymphoma xenograft model using single intravenous...
From the preceding, it is clear that oHSVs are safe in adults as agents for treatment of cancer by a variety delivery routes and offer several advantages. This large DNA virus does not integrate into host genome substantial amount its essential infection replication tumor cells. offers potential foreign therapeutic gene to cells facilitate efficacy improving percolation through tissue engendering strong immune response infected To extent pre-existing immunity may hasten clearance virus,...
High Mobility Group Box 1 (HMGB1) is a multifunctional protein that plays various roles in the processes of inflammation, cancer, and other diseases. Many reports document abundant HMGB1 release following infection with oncolytic viruses (OVs). Further, groups including previous from our laboratory highlight synergistic effects OVs chemotherapy drugs. Here, we show virus-free supernatants have varying cytotoxic potential, actively secreted by two established fibroblast cell lines (NIH 3T3...
Oncolytic engineered herpes simplex viruses (HSVs) possess many biologic and functional attributes that support their use in clinical trials children with solid tumors. Tumor cells, an effort to escape regulatory mechanisms would impair growth progression, have removed protected them from virus infection eventual virus-mediated destruction. Viruses exploit this weakness, like mutant HSV, can be safely employed as tumor cell killers, since normal cells retain these antiviral strategies. Many...
Background Oncolytic virotherapy (OV) is an immunotherapy that incorporates viral cancer cell lysis with engagement of the recruited immune response against cells. Pediatric solid tumors are challenging targets because they contain both inert environment and a quiet antigenic landscape, making them more resistant to conventional OV approaches. Further complicating this, herpes simplex virus suppresses host gene expression during infection. Methods We therefore developed multimodal oncolytic...
Herpes simplex virus (HSV) is one of the many viruses that have been modified or adapted for oncolytic purposes. There are two serotypes HSV, HSV-1 and HSV-2. The majority HSVs, including T-VEC which has recently approved by US Food Drug Administration (FDA) clinical use in treating late stage melanoma patients, derived from HSV-1. Recently, we others developed several HSV-2 based viruses. During our vitro characterization both (Baco-1 FusOn-H2 HSV-2), noticed there a subpopulation cancer...
We previously reported that the DNA alkylator and transcriptional-blocking chemotherapeutic agent trabectedin enhances oncolytic herpes simplex viroimmunotherapy in human sarcoma xenograft models, though mechanism remained to be elucidated. Here we report disrupts intrinsic cellular anti-viral response which increases viral transcript spread throughout tumor cells. also extended our synergy findings syngeneic murine are poorly susceptible virus infection. In absence of robust replication,...
We previously reported that the DNA alkylator and transcriptional-blocking chemotherapeutic agent trabectedin enhances oncolytic herpes simplex viroimmunotherapy in human sarcoma xenograft models, though mechanism remained to be elucidated. Here we report disrupts intrinsic cellular antiviral response which increases viral transcript presence tumor cells. also extended our synergy findings syngeneic murine are poorly susceptible virus infection. In absence of robust replication, found...
Patients with osteosarcoma (OS), a debilitating pediatric bone malignancy, have limited treatment options to combat aggressive disease. OS thrives on insulin growth factor (IGF)-mediated signaling that can facilitate cell proliferation. Previous efforts target IGF-1R were mostly unsuccessful, likely due compensatory through alternative splicing of the receptor (