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Recent clinical trials utilizing Interferon-alpha (IFN) in combination with chemoradiation have demonstrated significant improvements in the survival of patients with pancreatic cancer. However, efficacy was limited by the systemic toxicity of IFN and low intratumoral levels of the cytokine. We sought to address these drawbacks by using an Oncolytic Adenovirus expressing IFN (OAd-hamIFN) in combination with chemotherapy and/or radiation in regimens mimicking the IFN-based therapies used in clinical trials. IFN expressed from OAd-hamIFN potentiated the cytotoxicity of radiation and chemotherapy (5-FU, Gemcitabine, and Cisplatin), and enhanced pancreatic cancer cell death in both and experimental settings. Notably, synergism was demonstrated in therapeutic groups that combined the interferon-expressing oncolytic virus with chemotherapy and radiation. In an immunocompetent hamster model, treatment regimens combining oncolytic virus therapy with 5-FU and radiation demonstrated significant tumor growth inhibition and enhanced survival. This is the first study to report synergism between an IFN-expressing oncolytic adenovirus and chemoradiation-based therapies. When combined with an IFN-expressing OAd, there is a significant enhancement of radiation and especially chemoradiation, which may broaden the application of this new therapeutic approach to the pancreatic cancer patients who cannot tolerate existing chemotherapy regimens.
This article was published in the following journal.
Oncolytic virus therapy is a promising new option for cancer. It utilizes genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming norm...
Oncolytic viruses represent a unique type of agents that combine self-amplification, lytic and immunostimulatory properties against tumors. A local and locoregional clinical benefit has been demonstra...
Pre-existing anti-adenovirus (Ad) neutralizing antibodies (AdNAbs) are a major barrier in clinical gene therapy using Ad vectors and oncolytic Ads; however, it has not been fully elucidated which Ad c...
Uveal melanoma (UM) is a severe human malignancy with a high mortality rate, as well as high metastasis and recurrence potential. The active mutation of G protein subunit alpha q (GNAQ) or G protein s...
Chemotherapy-induced peripheral neuropathy and radiation-induced brachial plexopathy are extremely debilitating conditions which can occur after treatment of malignancy. Unfortunately, the diagnosis c...
This study involves patients with a type of cancer called HER2 (Human Epidermal Growth Factor Receptor 2) positive cancer. Because there is no standard treatment for this cancer at this ti...
Oncolytic adenovirus for pediatric naive DIPG, to be infused after tumor biopsy through the same trajectory in the cerebellar peduncle.
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The primary objective of this phase 1 trial is to determine the dose-dependent toxicity and maximum tolerated dose (MTD) of oncolytic adenovirus-mediated cytotoxic gene therapy in combinat...
The purpose of this study is to see if LOAd703 (an oncolytic adenovirus) can be safely given to patients with pancreatic cancer. The study will also evaluate whether or not intratumoral in...
The very first viral gene products synthesized after cells are infected with adenovirus. The E1 region of the genome has been divided into two major transcriptional units, E1A and E1B, each expressing proteins of the same name (ADENOVIRUS E1A PROTEINS and ADENOVIRUS E1B PROTEINS).
Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA).
Tumor-selective, replication competent VIRUSES that have antineoplastic effects. This is achieved by producing cytotoxicity-enhancing proteins and/or eliciting an antitumor immune response. They are genetically engineered so that they can replicate in CANCER cells but not in normal cells, and are used in ONCOLYTIC VIROTHERAPY.
Drug treatment designed to further diminish the disease toward complete remission following INDUCTION CHEMOTHERAPY. It helps to consolidate the gains during induction chemotherapy and may be followed by MAINTENANCE CHEMOTHERAPY.
Drug therapy given to augment or stimulate some other form of treatment such as surgery or radiation therapy. Adjuvant chemotherapy is commonly used in the therapy of cancer and can be administered before or after the primary treatment.
Pancreatitis Acute pancreatitis is inflammation of the pancreas caused by the release of activated pancreatic enzymes. Common triggers are biliary tract disease and chronic heavy alcohol intake. Diagnosis is based on clinical presentation...
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Clinical trials are a set of procedures in medical research conducted to allow safety (or more specifically, information about adverse drug reactions and adverse effects of other treatments) and efficacy data to be collected for health interventions (e.g...