A5008818696- Virus-based gene therapy research
- Glioma Diagnosis and Treatment
- Cancer Research and Treatments
- Epigenetics and DNA Methylation
- Viral Infectious Diseases and Gene Expression in Insects
- interferon and immune responses
- Cancer, Hypoxia, and Metabolism
- Cytomegalovirus and herpesvirus research
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Pneumonia and Respiratory Infections
- Herpesvirus Infections and Treatments
- Viral Infections and Immunology Research
- RNA modifications and cancer
- Cancer-related gene regulation
- Bacterial Infections and Vaccines
- Immune Cell Function and Interaction
- Cancer Mechanisms and Therapy
- Chromatin Remodeling and Cancer
- Animal Genetics and Reproduction
- Neonatal Health and Biochemistry
- Signaling Pathways in Disease
- Immune cells in cancer
- PARP inhibition in cancer therapy
- Immunotherapy and Immune Responses
The University of Texas MD Anderson Cancer Center
2023-2024
The University of Texas Health Science Center at Houston
2023-2024
Johns Hopkins Medicine
2021-2022
Johns Hopkins University
2021-2022
University of Baltimore
2022
Indian Institute of Technology Bombay
2021
Oncolytic viruses are a promising treatment for patients with high-grade gliomas, but neutralizing antibodies can limit their efficacy in prior virus exposure or upon repeated injections. Data from previous clinical trial using the oncolytic adenovirus Delta-24-RGD showed that generation of anti-viral may affect long-term survival glioma patients. Past studies have examined effects during systemic injections, largely overlooked impact local injections into brain. We found immunoglobulins...
Reprograming of cellular metabolism is a hallmark cancer. Altering allows cancer cells to overcome unfavorable microenvironment conditions and proliferate invade. Medulloblastoma the most common malignant brain tumor children. Genomic amplification MYC defines subset poor-prognosis medulloblastoma. We performed comprehensive metabolic studies human MYC-amplified medulloblastoma by comparing profiles in three different conditions-in vitro, flank xenografts orthotopic cerebellum. Principal...
Currently, there is a lack of effective therapies for the majority glioblastomas (GBMs), most common and malignant primary brain tumor. While immunotherapies have shown promise in treating various types cancers, they had limited success improving overall survival GBM patients. Therefore, advancing treatment requires deeper understanding molecular cellular mechanisms that cause resistance to immunotherapy. Further insights into innate immune response are crucial developing more potent...
Intensive chemotherapeutic regimens with craniospinal irradiation have greatly improved survival in medulloblastoma patients. However, markedly differs among molecular subgroups and their biomarkers are unknown. Through unbiased screening, we found Schlafen family member 11 (SLFN11), which is known to improve response DNA damaging agents various cancers, be one of the top prognostic markers medulloblastomas. Hence, explored expression functions SLFN11 medulloblastoma.SLFN11 for each subgroup...
Host cellular barriers have innate immune defenses to restrict microbial passage into sterile compartments. Here, by focusing on the blood-brain barrier endothelium, we investigated mechanisms that enable Streptococcus pneumoniae traverse through host barriers.
<h3>Background</h3> Viroimmunotherapy has emerged as a promising strategy to treat patients with glioblastoma (GBM). Our group developed Delta-24-RGD, an oncolytic adenovirus that been tested in clinical trials for adult and pediatric brain tumors showing encouraging 20% response.<sup>1–3</sup> The dual mechanism of action the viruses encompasses direct tumor cell lysis indirect anti-tumor immune response. To improve rate responses, we generated Delta-24-RGDOX, armed version expressing...
<h3>Background</h3> Glioblastoma multiforme (GBM) is the most common primary malignancy of central nervous system. GBM patients often face dismal prognoses despite aggressive treatments, highlighting urgent need for innovative therapeutic approaches. Oncolytic virotherapy (OV) utilizing Delta-24-RGD has emerged as a promising strategy, with recent clinical trials (NCT00805376, NCT03178032, and NCT02798406)<sup>1–3</sup> showing encouraging responses in subsets patients. However, several...
<h3>Background</h3> To address the unmet medical needs for patients with advanced metastatic solid tumors, CAR T cells and oncolytic viruses (OVs) are being tested clinically. Unlike their remarkable success in hemopoietic malignancies, effect of tumors is moderate. We have reported that third-generation adenovirus (OA), Delta-24-RGDOX, which expresses immune co-stimulator OX40 ligand (OX40L), more potent to elicit anti-tumor immunity than second-generation OA Delta-24-RGD sustains systemic...
Abstract BACKGROUND H3K27-altered pediatric diffuse midline glioma (DMG) is a highly aggressive type of brain tumor with 5-year survival rate less than 2%. Conventional treatments are restricted to palliative radiation therapy. Therefore, effective urgently needed. Results from recent phase I clinical trial for Diffuse Intrinsic Pontine Glioma showed that intratumoral administration Delta-24-RGD oncolytic adenovirus in combination improves without unwanted toxicity. Based on the rationale...
<h3>Background</h3> Viroimmunotherapy is an emerging biotherapeutic strategy utilizing oncolytic viruses (OVs) to mediate tumor destruction through direct oncolysis and instigation of anti-tumor immunity. There growing interest in viroimmunotherapy for pediatric brain tumors due its ability enhance immune responses non-inflamed tumors. Our lab developed the adenovirus Delta-24-RGD, which has been tested Phase I clinical trial (NCT03178032) as front-line therapy brainstem diffuse midline...
<h3>Background</h3> Previous trials testing oncolytic adenovirus Delta-24-RGD in malignant gliomas has shown encouraging results. Since viruses can stimulate immune reactions against both virus and tumor, immunodominance of viral antigens may prevent the preferred generation tumor-specific clones. In this work, we tested extent to which nanoparticle-induced tolerance shift focus system tumor improves therapeutic outcome. <h3>Methods</h3> Genomic DNA from surgical samples 9 glioma patients...
<h3>Background</h3> Oncolytic virotherapy is a special case of cancer immunotherapy that mounts significant inflammatory immune response along with oncolysis. We recently demonstrated Delta-24-RGD, an oncolytic adenovirus, can be safely combined radiotherapy to treat pediatric Diffuse Intrinsic Pontine Glioma in phase I clinical trial (NCT03178032). In this trial, combining Delta-24-RGD increased the median survival patients 17.8 months. Histone hyperacetylation epigenetic signature Midline...
Abstract Diffuse midline glioma (DMG) remains a devastating pediatric brain tumor without effective treatment. In recent clinical trial, we demonstrated the feasibility and efficacy of Delta-24-RGD oncolytic virus combined with radiation therapy in patients newly diagnosed diffuse intrinsic pontine gliomas (NCT03178032). Because adenoviral protein E1A binds to P300 redirects acetylation upon infection, hypothesized that combining adenoviruses inhibitors will cause remarkable shifting...
Abstract Phase 1 and 2 clinical trials of our oncolytic adenovirus Delta-24-RGD for patients with recurrent malignant gliomas have demonstrated its safety efficacy, showed that 20% the experienced long-term tumor remissions often associated inflammatory responses infiltration lymphocytes. Based on preliminary data, we expected most frequent tumor-infiltrating CD8+ T cell clones will target adenoviral hexon, a single virus-specific clone representing up to 5% total population. Competition...
Abstract Diffuse midline gliomas (DMGs) are among the most frequent and lethal pediatric tumors. The standard of care for DMGs is palliative, resulting in a median survival 12 months. Viroimmunotherapy an emerging alternative treatment these Our group developed platform oncolytic adenoviruses that was translated to clinic. Specifically, Delta-24-RGD recently tested Phase I clinical trial patients with newly diagnosed DMG (NCT03178032) encouraging results. To further stimulate immune arm this...
Abstract Glioblastoma (GBM) poses a significant therapeutic challenge in oncology. Recent clinical trials have shown the feasibility of virotherapy to treat patients with GBM. Our laboratory developed an oncolytic adenovirus termed Delta-24-RGD that has been tested for recurrent GBM encouraging results (NCT00805376, NCT02798406). These studies, together preclinical data, showed efficacy was due direct tumor cell oncolysis and indirect activation anti-tumor immune response. To further...
Abstract Accumulating evidence show that the interaction between oncolytic viruses (OVs) and host immune system plays an essential role in cancer virotherapy. Compared to lytic potency of OVs, enhancement OV-mediated anti-tumor immunity has become a more attractive strategy improve OV efficacy. To this end, we have reported third-generation adenovirus (OA), Delta-24-RGDOX, which expresses co-stimulator OX40 ligand (OX40L), is potent elicit than second-generation OA Delta-24-RGD. Since IL-15...
Abstract Despite aggressive therapeutic interventions, glioblastoma patients face a median survival of seven months after tumor recurrence. Alarmingly, there has been no improvement to the standard care for two decades, and still receive toxic doses radiation chemotherapy, rendering many unable perform daily functions. An emerging approach, oncolytic virotherapy (OV) using Delta-24-RGD, is gaining traction due recent clinical trials (NCT00805376, NCT03178032, NCT02798406) exhibiting robust...
ABSTRACT BACKGROUND Oncolytic adenoviruses, such as Delta-24-RGD, show promise a potential breakthrough in treating patients with high-grade gliomas. However, their effectiveness against gliomas can be hindered by the presence of neutralizing antibodies. METHODS Production human antibodies adenoviruses was assessed two cohorts malignant treated Delta-24-RGD phase 1 clinical trial. Sera containing were also obtained from mice immunized intramuscular injections wild-type Ad5. Chimeric...
Abstract Diffuse Midline Glioma, DMG, is one of the worst forms pediatric brain tumors and associated with a 100% mortality rate. unlike other types tumors, exists in hypomethylated epigenetic state. In this study, we investigate contribution Ten Eleven Translocation (TET) enzymes towards unique landscape. The TET which reduce 5methylcytosine (5mC) to 5hydroxymethylcytosine (5hmC) are essential for removing methylation marks genome. our previous studies, saw that there an increased...
Abstract Reprograming of cellular metabolism is a hallmark cancer. The metabolic alterations in cancer cells not only defined by series genetic mutations, but also reflecting the crosstalk between and other factors microenvironment. Altering allows to overcome unfavorable conditions, proliferate invade. Medulloblastoma most common malignant brain tumor children. Genomic amplification MYC subset poor-prognosis medulloblastoma. However, high amplified medulloblastoma subgroup remains...
Abstract Atypical teratoid rhabdoid tumors (ATRTs) are fatal pediatric brain that warrant improved therapies urgently. ATRTs characterized by loss of INI1, a subunit the SWI/SNF chromatin-remodeling complex. grow aggressively despite majority primary expressing p53, suggesting inactivation this tumor suppressor pathway. Reactivation p53 could be potential therapeutic strategy for inhibiting ATRT growth. Our laboratory specializes in researching mechanisms contributing to pathogenesis and...
Abstract Diffuse Intrinsic Pontine Glioma (DIPG) is one of the worst forms pediatric brain tumors, with a 100% mortality-rate. A prominent mutation observed in them lysine to methionine change histone3 which causes trapping repressive-chromatin-complex, leading genome-level hypomethylation, affecting global epigenetic-regulation. Ten-Eleven Translocation (TET) proteins are alpha-ketoglutarate (α-KG) dependent dioxygenases that mediate conversion 5-methylcytosine 5-hydroxymethylcytosine...