Hong Jiang

University of Texas MD Anderson Cancer Center | MD Anderson · Department of Neuro Oncology

BACKGROUND H3K27-altered pediatric diffuse midline glioma (DMG) is a highly aggressive type of brain tumor with a 5-year survival rate of less than 2%. Conventional treatments are restricted to palliative radiation therapy. Therefore, effective treatments are urgently needed. Results from a recent phase I clinical trial for Diffuse Intrinsic Pontin...

BACKGROUND Pediatric high-grade (pHGGs) and diffuse midline gliomas (DMGs) patients have the worst survival rates in childhood cancer. The oncolytic adenovirus Delta-24-RGD and the imipridone ONC201 are two of the most promising therapeutic agents in the field, having demonstrated safety and effectiveness in clinical trials. Therefore, we evaluated...

Oncolytic viruses (OVs) are biological therapeutic agents that selectively destroy cancer cells while sparing normal healthy cells. Besides direct oncolysis, OV infection induces a proinflammatory shift in the tumor microenvironment and the release of tumor‐associated antigens (TAAs) that might induce an anti‐tumor immunity. Due to their immunostim...

Background Pediatric high-grade gliomas (pHGGs), including diffuse midline gliomas (DMGs), are aggressive pediatric tumors with one of the poorest prognoses. Delta-24-RGD and ONC201 have shown promising efficacy as single agents for these tumors. However, the combination of both agents has not been evaluated. Methods The production of functional v...

Glioblastoma (GBM) is the most aggressive malignant primary brain tumor worldwide. Current standard-of-care treatments allow for a median survival of 12 to 18 months. GBM has a poor survival prognosis, observing less than 6% of patients surviving 5 years post-diagnosis. Among recent treatment advancements, the oncolytic adenovirus Delta-24-RGDOX ar...

Glioblastoma, the most common primary brain tumor, has a 6.8% survival rate 5 years post diagnosis. Our team developed an oncolytic adenovirus with an OX-40L expression cassette named Delta-24-RGDOX. While studies have revealed the interaction between the gut microbiota and immunotherapy agents, there are no studies linking the gut microbiota with...

Currently, there is a lack of effective therapies for the majority of glioblastomas (GBMs), the most common and malignant primary brain tumor. While immunotherapies have shown promise in treating various types of cancers, they have had limited success in improving the overall survival of GBM patients. Therefore, advancing GBM treatment requires a d...

Oncolytic virotherapy holds great potential to treat high-grade gliomas by harnessing virus-mediated oncolysis to stimulate anti-tumor immune responses. However, the efficacy of oncolytic adenoviruses can be hampered by neutralizing antibodies. In this study, we examined sera obtained from a phase 1 clinical trial using oncolytic adenovirus Delta-2...

Despite aggressive therapies, the median survival for glioblastoma (GBM) patients remains just 7-months after tumor progression. Oncolytic virotherapy is a promising approach to reprogramming the immunosuppressed microenvironment of GBMs facilitating anti-tumor immunity. Delta-24-RGD is an oncolytic adenovirus that has shown favorable results in ph...

Background Despite aggressive therapeutic interventions, glioblastoma (GBM) patients face a median survival rate of just seven months after tumor progression. To address these obstacles, oncolytic-virotherapy has emerged as a propitious approach, offering the potential to reprogram the immunosuppressed microenvironment of GBMs and enhance anti-tumo...

BACKGROUND Oncolytic virotherapy is emerging as a novel therapeutic strategy for glioblastoma (GBM). DNX-2401, an oncolytic adenovirus with selective replication and enhanced infectivity in tumor cells, showed anti-tumor effect in a previous clinical trial for recurrent GBM. The combination of DNX-2401 and Temozolomide (TMZ) has shown a synergistic...

BACKGROUND Oncolytic immunovirotherapy is emerging as a potential therapeutic approach in neuro-oncology. The oncolytic adenovirus DNX-2401, genetically engineered for selective replication and enhanced infectivity in tumor cells, has shown efficacy in adult patients with recurrent glioblastoma (GBM). In order to overcome the immunosuppressive brai...

Background: Endovascular selective intra-arterial (ESIA) infusion of cellular oncotherapeutics is a rapidly evolving strategy for treating glioblastoma. Evaluation of ESIA infusion requires a unique animal model. Our goal was to create a rabbit human GBM model in order to test IA infusions of cellular therapies and to test its usefulness by employ...

BACKGROUND Oncolytic adenoviruses, such as Delta-24-RGD, show promise as 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 of human neutralizing antibodies against adenoviruses was assessed in two cohorts...

Diffuse Midline Gliomas (DMG) are very aggressive brain tumors that arise in the brainstem of children. The prognosis of these patients is still dismal, with an overall survival of less than one year. DMG tumors are poorly infiltrated by the immune system, and therefore in this project, we propose the use of the oncolytic adenovirus Delta-24-RGDOX...

Immune-mediated anti-tumoral responses, elicited by oncolytic viruses and augmented with checkpoint inhibition, may be an effective treatment approach for glioblastoma. Here in this multicenter phase 1/2 study we evaluated the combination of intratumoral delivery of oncolytic virus DNX-2401 followed by intravenous anti-PD-1 antibody pembrolizumab i...

Gastric cancer is the third leading cause of cancer-related mortality worldwide, and current standard-of-care treatment allows for a 5-year survival rate of 20%. Newer treatments against solid tumors include an oncolytic adenovirus armed with T-cell activator OX40L, named Delta-24-RGDOX, which expresses the positive immune checkpoint OX-40L. While...

Purpose of the work: Pediatric High Grade Gliomas (pHGGs) and Diffuse Midline Gliomas (DMGs) are two of the most aggressive tumors developed during childhood. Its poor overall survival emphasizes the need of alternative treatments. ONC201, an imipiridone small molecule, and the oncolytic virus Delta-24-RGD have shown safety and effectiveness in pre...

The median survival for glioblastoma (GBM) patients is 12-15 months, with a five-year survival rate of less than 10% despite aggressive treatment with surgery, radiotherapy, and chemotherapy. Oncolytic virotherapy is emerging as a promising approach to reprogramming the immunosuppressed microenvironment of GBMs and restoring anti-tumor immunity. De...

INTRODUCTION Poor outcomes for glioblastoma (GBM) are partly due to the inability to deliver therapeutic agents to the tumor because of the blood brain barrier (BBB) as well as ineffective agents. We have evaluated bone marrow-derived mesenchymal stem cells (MSCs) as transport vehicles of biological therapeutics, particularly Delta-24-RGD (D24), an...

Cancer cell heterogeneity and immunosuppressive tumor microenvironment (TME) pose a challenge in treating solid tumors with adoptive cell therapies targeting limited tumor-associated antigens (TAA), such as chimeric antigen receptor T-cell therapy. We hypothesize that oncolytic adenovirus Delta-24-RGDOX activates the TME and promote antigen spread...

Despite advances in treatment options, the clinical outcomes of pediatric patients with advanced solid tumors have hardly improved in decades, and alternative treatment options are urgently needed. Innovative therapies, such as chimeric antigen receptor (CAR) T cells and oncolytic viruses (OVs), are currently being evaluated in both adults and chil...

Oncolytic virotherapy shows great potential for treating brain tumors and other solid tumors that metastasize to the brain. A phase I clinical trial testing the oncolytic adenovirus Delta-24-RGD (DNX-2401) in patients with recurrent malignant gliomas demonstrated significant clinical benefits for a subset of patients, and another phase I trial test...

The median survival for GBM patients is 15 months with a five-year survival rate of less than 10%. Current conventional and experimental treatments, including immune checkpoint blockade, have not improved outcomes in the vast majority of glioma patients. Oncolytic viruses (OVs) are designed to specifically infect and lyse cancer cells to elicit an...

Tumor-targeting biological therapies, including adoptive T cell therapy (ACT) and oncolytic viruses, are being tested clinically to address the challenges in treating advanced solid tumors with heterogeneity and immune suppressive microenvironment (TME). Since complementary properties of these two approaches have been observed, we hypothesize that...

Oncolytic viruses are considered part of immunotherapy and have shown promise in preclinical experiments and clinical trials in a small fraction of patients. To improve the response rate, it is necessary to reshape the tumor microenvironment that shields the tumor from the immune system of the patient. We engineered Delta-24-RGDOX (DNX-2440), an on...

Background Within Diffuse Midline Gliomas, Diffuse Intrinsic Pontine Glioma (DIPG) is the principal cause of non-accidental pediatric deaths. Although gold-standard treatments have improved, the outcome for children with DIPGs remains poor pointing to the need for alternative therapies. In this sense, we have previously demonstrated that the oncoly...

Background Oncolytic viruses are considered part of immunotherapy and have shown promise in preclinical experiments and clinical trials. Results from these studies have suggested that tumor microenvironment remodeling is required to achieve an effective response in solid tumors. Here, we assess the extent to which targeting specific mechanisms unde...

Background: Pediatric patients with diffuse intrinsic pontine glioma (DIPG) have a poor prognosis, with a median survival of less than 1 year. Oncolytic viral therapy has been evaluated in patients with pediatric gliomas elsewhere in the brain, but data regarding oncolytic viral therapy in patients with DIPG are lacking. Methods: We conducted a...

Recent clinical observations that some coronavirus infections induced complete remissions in lymphoma patients emphasized again the potential of cancer virotherapy. Infection of cancer cells with oncolytic viruses reshapes the tumor microenvironment by activating anti-viral and anti-tumor immunity. A phase 1 clinical trial using oncolytic adenoviru...

Purpose of Study: Diffuse Midline Gliomas (DMG) are aggressive pediatric brain tumors that arise in the brainstem of children, with a peak of incidence between 5-10 years old. The median survival of DMG patients is only 9 months, being the leading cause of pediatric death caused by a brain tumor. On this project we set to characterize the efficacy...

Oncolytic viruses are a promising experimental treatment for solid tumors. Recently, several phase 1 clinical trials have reported encouraging therapeutic effects of oncolytic viruses in adult and pediatric patients with malignant gliomas. To further improve the therapeutic outcome of viroimmunotherapy, we have developed Delta-24-RGDOX (DNX-2440),...

CAR T therapy greatly improves the survival of patients with hematological malignancies. But its effect in solid tumors is suboptimal. Intratumoral injections of oncolytic viruses, including Delta-24-RGDOX (DNX-2440) from our group, directly lyse cancer cells and activate tumor microenvironment, leading to adaptive antitumor immunity. To take advan...

Purpose of the work: Pediatric High Grade Gliomas (pHGGs), including Diffuse Midline Gliomas (DMGs), are very aggressive solid tumors developed during childhood with a poor overall survival underscoring the need for effective treatments. The adenovirus Delta-24RGD and the imipridone ONC201 have demonstrated safety and effectiveness in preclinical m...

Viroimmunotherapy aims to infect cancer cells to elicit anti-tumor immune responses. In clinical trials, glioma treatment with oncolytic viruses induced durable clinical responses in a small fraction of patients. To improve the percentage of responders, it is necessary to reshape the tumor microenvironment that shields the tumor from the immune sys...

With a 2-year survival less than 20%, Diffuse Intrinsic Pontine Glioma (DIPG) is the principal cause of pediatric death. Despite recent advances in the current treatments, the outcome for children with DIPGs remains dismal. Since the approval of T-VEC for melanoma by the FDA, oncolytic adenoviruses have emerged as a promising therapeutic strategy f...

The COVID-19 pandemic has produced a new global challenge for patients with cancer. The disease and the immunosuppression induced by cancer therapies have generated a perfect storm of conditions to increase the severity of the symptoms and worsen the prognosis. However, a few clinical reports showcased the power of viruses to induce remission in so...

Diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors, and patient survival has not changed despite many therapeutic efforts, emphasizing the urgent need for effective treatments. Here, we evaluated the anti-DIPG effect of the oncolytic adenovirus Delta-24-ACT, which was engineered to express the costimulatory ligand 4-1BB...

Glioblastoma is the most common primary malignant brain neoplasm and it remains one of the most difficult-to-treat human cancers despite decades of discovery and translational and clinical research. Many advances have been made in our understanding of the genetics and epigenetics of gliomas in general; yet, there remains an urgent need to develop n...

Osteosarcoma is an aggressive bone tumor occurring primarily in pediatric patients. Despite years of intensive research, the outcomes of patients with metastatic disease or who do not respond to therapy have remained poor and have not changed in the last 30 years. Oncolytic virotherapy is becoming a reality to treat local and metastatic tumors whil...

Immune-related therapies have revolutionized the management of cancer. Oncolytic viruses are now considered part of the immunotherapy armamentarium and have shown promise in clinical trials of patients with glioblastoma. These studies have suggested that tumor microenvironment remodeling is required to achieve an effective response in solid tumors....

BACKGROUND Diffuse intrinsic pontine glioma (DIPG) is the most lethal pediatric brain tumor. Median overall survival (OS) with standard of care radiation therapy (RT) is approximately 8-10 months and 2-year survival is < 10%. A Phase 1 single-center study was conducted to evaluate the oncolytic adenovirus, DNX-2401 (tasadenoturev), followed by RT f...

Background Diffuse Midline Gliomas (DMG) are aggressive pediatric brain tumors that arise in the brainstem of children between 5–10 years old. DMGs are the leading cause of pediatric death caused by a brain tumor, with a median survival of only 9 months. 1 2 We have previously shown that the administration of the oncolytic adenovirus Delta-24-RGD i...

Background Unlike its remarkable success in treating hematological malignancies, adoptive T cell therapy (ACT), such as CAR T therapy, targeting limited tumor-associated antigens (TAAs) is far less effective in patients with heterogeneous solid tumors. Oncolytic viruses, including oncolytic adenovirus Delta-24-RGDOX from our group [1, 2], are emerg...

Objective: Delta-24-RGD is an oncolytic adenovirus that is capable of replicating in and killing human glioma cells. Although intratumoral delivery of Delta-24-RGD can be effective, systemic delivery would improve its clinical application. Bone marrow-derived human mesenchymal stem cells (BM-hMSCs) obtained from healthy donors have been investigat...

Background Glioblastoma (GBM) is a devastating primary brain tumor with a highly immunosuppressive tumor microenvironment, and treatment with oncolytic viruses (OVs) has emerged as a promising strategy for these tumors. Our group constructed a new OV named Delta-24-ACT, which was based on the Delta-24-RGD platform armed with 4-1BB ligand (4-1BBL)....

p>Gastric cancer is the third leading cause of cancer-related mortality worldwide, with a 5-year survival rate of 30% in the US despite standard treatment. Black, Asian, and non-white Hispanic populations have a 40-50% higher risk of gastric cancer than white people. The poor prognosis and limited therapies associated with gastric cancer has led us...

Oncolytic virotherapy and adoptive T cell therapy (ACT) are promising strategies for cancer treatment, but both are underdeveloped into routine clinical interventions for solid tumors. We reported previously that localized treatment with oncolytic adenovirus Delta-24-RGDOX (DNX-2440), which expresses immune co-stimulator OX40 ligand, stimulated tum...

Metastatic breast cancer is the second leading cause of cancer related death among women. Although, conventional therapies such as surgery, adjuvant and neoadjuvant therapies have shown promising outcomes in preclinical and clinical settings, long-term survival rates remain unacceptably low for patients with recurrent disease or disseminated metast...

p>Oncolytic viruses are a new form of cancer immunotherapy that harnesses the combined abilities of the virus to directly lyse cancer cells and to induce immunogenic environments to activate anti-tumor immunity. Our oncolytic adenovirus Delta-24-RGD has demonstrated significant clinical benefits for a subset of patients with recurrent malignant gli...

p>Diffuse Intrinsic Pontine Glioma (DIPG) is the leading cause of pediatric death by brain tumors with a median survival of only 9 months, in spite of the current standard of therapy which includes radiation. The purpose of our study is to explore the use of oncolytic adenoviruses as a new therapeutic modality. Our group is leading a phase I clinic...

p>Malignant gliomas are devastating diseases that require new and more effective treatments. To improve clinical outcomes, our laboratories have developed an oncolytic adenovirus armed with the T-cell activator OX40L, named Delta-24-RGDOX. Here, we evaluated changes to gut microbiome in glioma bearing mice treated with viroimmunotherapy. GL261 glio...

Immune enhancement of virotherapy by reshaping the tumor immune landscape may improve its success rates. IDO, an IFNγ inducible tryptophan catabolizing enzyme, is upregulated in glioblastoma, correlating with poor prognoses. IDO-mediated tryptophan depletion in the tumor-microenvironment decreases viral replication and diminishes cell proliferation...

With a 2-year survival less than 20%, Diffuse Intrinsic Pontine Glioma (DIPG) is the principal cause of pediatric death. Despite recent advances in the current treatments, the outcome for children with DIPGs remains dismal. Since the approval of T-VEC for melanoma by the FDA, oncolytic adenoviruses have emerged as a promising therapeutic strategy f...

Diffuse Intrinsic Pontine Gliomas (DIPG) are aggressive pediatric brain tumors that arise in the pons of children, being the leading cause of pediatric death caused by cancer. We have previously demonstrated that Delta-24-RGD administration is safe and efficacious in DIPG preclinical models, indicating that it could be a good candidate as therapeut...

Pediatric High Grade Gliomas (pHGGs), including Diffuse Midline Gliomas (DMGs), are aggressive pediatric tumors with a poor overall survival. In the last years, ONC201 has emerged as a promising agent in the field of pediatric brain tumors. Another interesting approach is virotherapy; Delta-24-RGD, which is an oncolytic virus, has demonstrated safe...

Background A Phase 1, single center study is ongoing to evaluate the conditionally replicative oncolytic adenovirus, DNX-2401 (tasadenoturev), followed by radiotherapy (RT) in pediatric patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG). Methods Patients 1–18 years with newly diagnosed DIPG with no prior treatment, Lansky/Karnof...

Background: Oncolytic adenoviruses are promising new treatments against solid tumors, particularly for glioblastoma (GBM), and preclinical models are required to evaluate the mechanisms of efficacy. However, due to the species selectivity of adenovirus, there is currently no single animal model that supports viral replication, tumor oncolysis, and...

Cancer virotherapy is a paradigm-shifting treatment modality based on virus-mediated oncolysis and subsequent antitumor immune responses. Clinical trials of currently available virotherapies showed that robust antitumor immunity characterizes the remarkable and long-term responses observed in a subset of patients. These data suggest that future the...

Delta-24–based oncolytic viruses are conditional replication adenoviruses developed to selectively infect and replicate in retinoblastoma 1 (Rb)–deficient cancer cells but not normal cell with intact Rb1 pathways. Over the years, there has been a significant evolution in the design of Delta-24 based on a better understanding of the underlying basis...

Purpose: Atypical teratoid/rhabdoid tumors (AT/RTs) and primitive neuroectodermal tumors (CNS-PNETs) are pediatric brain tumors with poor survival and life-long negative side effects. Here, the aim was to characterize the efficacy and safety of the oncolytic adenovirus Delta-24-RGDs, which selectively replicates in and kills tumor cells. Experime...

BACKGROUND Delta-24-RGD, an oncolytic adenovirus, shows promise against glioblastoma. To enhance virus delivery, we recently demonstrated that human bone marrow-derived mesenchymal stem cells loaded with Delta-24-RGD (hMSC-D24) can eradicate glioblastomas in mouse models. There are no studies examining the safety of endovascular selective intra-art...

Current therapies for atypical teratoid/rhabdoid tumors (AT/RTs) are suboptimal, resulting in a 2-year OS below 20% and the development of severe side effects. Therefore, we need to explore alternative therapeutic approaches for this disease. Since the virus Delta24-RGD has already demonstrated its efficacy and safety as a therapeutic agent for bra...

The objective of this trial is to determine the safety, tolerability, and toxicity of DNX-2401 in newly diagnosed DIPG patients (NCT03178032) followed by radiotherapy. Secondary endpoints are overall survival at 12 months, percentage of responses and induced immune response against tumor. Tumor biopsy was performed through the cerebellar peduncle,...

Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumour, being the leading cause of paediatric death caused by cancer. Despite all the advances made regarding effective therapies, the survival is dismal. Our lab has engineered the oncolytic virus Delta-24-ACT armed with the costimulatory ligand 41BBL in order to increase the antitumor...

Despite the advances in our understanding of pediatric diffuse midline gliomas (DMG) they remain the leading cause of pediatric death caused by cancer. Our group has demonstrated that the administration of Delta-24-RGD in DIPG models is safe and therapeutically efficacious. An on-going clinical trial with this virus has proven to be safe for these...

Cancer virotherapy is a paradigm-shifting treatment modality based on the capabilities of virus-mediated oncolysis to elicit an anti-tumor immune response. Phase 1 and 2 clinical trials have demonstrated the safety and efficacy of our oncolytic adenovirus DNX-2401 (Delta-24-RGD) for patients with recurrent malignant gliomas. While a subset of the p...

Despite our increased understanding of Diffuse Intrinsic Pontine Glioma (DIPG) the outcome remains dismal. Recently we showed that the virus Delta-24-RGD (DNX-2401 in the clinic) was effective in preclinical models of DIPG and had the ability to trigger an antitumor immune response. These data allowed us to propel a phase I clinical trial for newly...

Immune enhancement of virotherapy by reshaping the tumor immune landscape may improve its success rates. IDO, an IFNγ inducible tryptophan catabolizing enzyme, is upregulated in glioblastoma, correlating with poor prognoses. IDO-mediated tryptophan depletion in the tumor-microenvironment decreases proliferation and induces apoptosis of surrounding...

Oncolytic viruses have become promising therapeutic candidates to treat gliomas. Our group has developed Delta-24-ACT, an oncolytic adenovirus armed with the positive costimulatory ligand 4-1BBL which is capable to trigger the activation of T cells and thereby increase their antitumor immune response. Here we evaluate the anti-glioma effect of Delt...

Atypical teratoid/rhabdoid tumors (AT/RTs) and primitive neuroectodermal tumors of the central nervous system (CNS-PNET) are rare pediatric brain tumors affecting mainly infants and young children. Current therapies for these diseases are inefficient and often cause severe side effects; thus, new therapeutic strategies are urgently needed. Here, we...

Oncolytic adenoviruses, including Delta-24-RGD, target tumors by direct tumor cell oncolysis and by activation of an anti-tumor immune response. Due to the species selectivity of oncolytic adenoviruses, there is currently no single preclinical animal model of glioma that supports viral replication, tumor oncolysis, and virus-mediated immune respons...

OX40 ligand (OX40L)-expressing oncolytic adenovirus Delta-24-RGDOX induces efficacious antiglioma immunity in syngeneic intracranial glioma models of immunocompetent mice. It is unknown if the virus is effective to treat metastatic melanomas. To study the abscopal immunity against metastatic melanomas induced by intratumoral injection of the virus...

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults and prognosis is poor despite maximum therapeutic efforts. GBM is composed of heterogeneous cell populations, among which the glioma stem-like cells (GSCs) play an important role in tumor cell self-renewal and the ability to initiate and drive tumor growth and recurrence....

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults and prognosis is poor despite maximum therapeutic efforts. GBM is composed of heterogeneous cell populations, among which the glioma stem-like cells (GSCs) play an important role in tumor cell self-renewal and the ability to initiate and drive tumor growth and recurrence....

Glioblastoma diagnoses associate with upregulation of the immunosuppressive indoleamine-2,3-dioxygenase (IDO) enzyme, which correlates with poor prognoses. IDO inhibitors are immunometabolic adjuvants that can reverse protumor immunosuppression through increasing effector T-cell metabolism. To further stimulate antitumor T-cell activation, the OX40...

Atypical teratoid/rhabdoid tumors (AT/RTs) are rare pediatric brain tumors affecting mainly infants and young children. However, AT/RTs encompass almost 10% of death caused by pediatric brain tumors, and the 2-year overall survival for these children remains below 20%. For this reason, AT/RT ranks among the deadliest pediatric brain tumors. Therefo...

Immune checkpoint blockade has revolutionized cancer therapy; however the therapeutic benefit is limited to only a subset of patients with immunogenic (“hot”) tumors and is compromised by immune-related adverse events. We have reported the efficacy of oncolytic adenovirus Delta-24-RGDOX (DNX-2440) in syngeneic glioma mouse models. We hypothesized t...

Based on promising results of recent clinical trials using oncolytic viruses, virotherapy is evolving as an alternative to treat patients with malignant glioma. Our group developed the oncolytic adenovirus Delta-24-RGD (DNX-2401) that is being tested, alone or in combination with anti-PD1, in clinical trials for recurrent glioblastoma (NCT00805376;...

Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumor, being the leading cause of pediatric death caused by cancer. We previously showed that administration of the oncolytic virus Delta-24-RGD to DIPG murine models was safe and led to an increase in the median survival of these animals. However, not all the animals responded, undersc...

Delta-24-RGD (DNX-2401 in the clinic) has been tested for adult glioblastoma presenting a safe profile and promising efficacy. Our group has showed that the virus is safe and effective in preclinical models of pHGG and DIPG. Moreover, we showed that the virus is able to trigger an antitumor immune response. These results allowed us to propel a phas...

BACKGROUND Despite our increased understanding of the genetic make-up and new therapies for pediatric high grade glioma (pHGG) and Diffuse Intrinsic Pontine Glioma (DIPG) the outcome remains grim. Delta-24-RGD (DNX-2401 in the clinic) has been tested for adult glioblastoma presenting a safe profile and promising efficacy. Recently our group has sho...

BACKGROUND Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumor, being the leading cause of pediatric death caused by cancer. We previously showed that administration of the oncolytic virus Delta-24-RGD to DIPG murine models was safe and led to an increase in the median survival of these animals. However, not all the animals respond...

Purpose: Intratumoral injection of oncolytic adenovirus Delta-24-RGDOX induces efficacious antiglioma immunity in syngeneic glioma mouse models. We hypothesized that localized treatment with the virus is effective against disseminated melanomas. Experimental design: We tested the therapeutic effect of injecting Delta-24-RGDOX into primary subcut...

Pediatric High Grade Glioma (pHGG), including Diffuse Intrinsic Pontine Glioma (DIPG) are the most common and aggressive pediatric brain tumor. Despite great strides in the knowledge of their genetic make-up and new therapies, the outcome for children affected with these malignancies remains dismal. Therefore, it is critical to implement new therap...

Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors in desperate need of a curative treatment. Oncolytic virotherapy is emerging as a solid therapeutic approach. Delta-24-RGD is a replication competent adenovirus engineered to replicate in tumor cells with an aberrant RB pathway. Th...

Background: Viroimmunotherapy is evolving as a strong alternative for the standard treatment of malignant gliomas. Promising results from a recent clinical trial testing the anticancer effect of Delta-24-RGD in patients with glioblastoma suggested the induction of antitumoral immunity after viral administration. To further enhance the anti-glioma...

Pediatric high grade gliomas (pHGG), including diffuse intrinsic pontine gliomas (DIPGs), are aggressive tumors with a dismal outcome. Radiotherapy (RT) is part of the standard of care of these tumors; however, radiotherapy only leads to a transient clinical improvement. Delta-24-RGD is a genetically engineered tumor-selective adenovirus that has s...

Despite our increased understanding of the genetic make-up and new therapies for pediatric high grade glioma (pHGG) and Diffuse Intrinsic Pontine Glioma (DIPG) the outcome remains grim. Delta-24-RGD (DNX-2401 in the clinic) has been tested for adult glioblastoma presenting a safe profile and promising efficacy. The objective of this study was to ev...

Diffuse intrinsic pontine glioma (DIPG) is an aggressive and incurable pediatric brain tumor that arises in the brainstem. The median overall survival is only one year being the standard of treatment radiotherapy. Oncolytic adenoviruses have emerged as a promising therapeutic option for DIPG due to their specificity to tumor cells. Our clinical exp...

The immunosupressive microenvironment of glioblastoma (GB) is responsible for the resistance to therapies and its dismal prognosis. Several lines of evidence have linked brain tumor metabolism and immunoresistance with the presence of active metabolic pathways. In this regard, activation of indolamine-2,3-dioxygenase (IDO) in regulatory T-cells fav...