{"id":"05159","slug":"irf-2-expressing-oncolytic--05159","source":{"id":"05159","dataset":"techtransfer","title":"IRF-2-expressing Oncolytic Vaccinia Virus for Cancer Therapy","description_":"<p>Several immunotherapy protocols, such as immune checkpoint blockade (ICB) with antibodies, have seen significant success in recent years. However, it is clear that these therapies as single modalities or even in combination with each other are only effective for a subset of patients. Additionally, there is growing literature indicating the development of ICB resistance in patients who were previously responsive. <p><img src=\"https://s3.us-east-1.amazonaws.com/static.tto.c8e.ai/upitt/attachments/05159/0EMVv00000CLj4s.png\"></p></img>This chart shows tumor growth over 22 days when tumors were injected with phosphate buffered saline (red), a control (blue), or the IRF2 transcriptional modifier (green). </p><p><h2>Description</h2>A major determining factor of both response to ICB and development of ICB resistance is the Interferon (IFN) response in the tumor microenvironment (TME). IFNs appear to play opposing roles in tumor cells compared to immune cells. Researchers have used this opposing IFN response by modulating the transcription factors that regulate IFN response to improve immunotherapy by using a series of CRISPR/Cas9-based gene-edited syngeneic tumor cells to establish that tumor-intrinsic functions of specific IFN regulatory factors (IRFs) may underlie the opposing IFN response in tumor cells. A new IRF2-based transcriptional modifier that modulates IRF function in the TME using an engineered oncolytic virus has shown success in preclinical mouse models by forcing IRF2 expression in tumors by modulating IFN response and promoting a positive response to ICB. This is a conceptually new approach to tumor therapy using existing technology.</p><p><h2>Applications</h2>•\tImmunotherapy for cancer</p><p><h2>Advantages</h2>•\tUses a well-known oncolytic Vaccinia virus vehicle\r<br>•\tReduces risk of developing resistance to ICB therapy\r<br>•\tPromotes a positive response to ICB therapy</p><p><h2>Invention Readiness</h2>In vivo data</p><p><h2>IP Status</h2><a target=\"_blank\" href=\"https://patents.google.com/patent/US20220362317A1\">https://patents.google.com/patent/US20220362317A1</a></p><p></p>","tags":[],"file_number":"05159","collections":[],"meta_description":"IRF2-modified oncolytic vaccinia virus enhances tumor IFN signaling to boost and sustain immunotherapy responses.","image_url":"https://s3.us-east-1.amazonaws.com/static.tto.c8e.ai/upitt/attachments/05159/0EMVv00000CLj4s.png","apriori_judge_output":"{\"scores\":{\"novelty\":3.0,\"potential_impact\":3.0,\"readiness\":2.0,\"scalability\":2.0,\"timeliness\":2.0},\"weighted_score\":2.25,\"risks\":[\"Preclinical stage with limited in vivo data beyond mice\",\"IRF2 modulation may have safety/toxicity concerns\",\"Viral vector delivery and manufacturing scalability not demonstrated\",\"Competition with other ICB-resistance strategies\",\"Regulatory and translational risk transitioning oncolytic virus with immune-modulatory payload\"],\"one_sentence_take\":\"Promising concept with preclinical validation, but novelty and impact are moderate with significant translational/regulatory and scalability risks limiting near-term readiness.\"}","lead_inventor_name":"Saumendra Sarkar","technology_type":"Therapeutic Modality","technology_subtype":"Oncolytic Virus","therapeutic_areas":["Oncology"],"therapeutic_indications":[],"custom_tags":[],"all_tech_innovators":["Saumendra Narayan Sarkar","Stephen Howard Thorne"],"date_submitted":"2019-11-05"},"highlight":{},"matched_queries":null,"score":0.0}