1258 POSTER Phase I Clinical Trial of a Genetically Modified Oncolytic Vaccinia Virus GL-ONC1 With Green Fluorescent Protein Imaging

Biondo, Alexander W.; Pedersen, Jan; Karapanagiotou, Eleni; Tunariu, Nina; Mansfield, David; Sassi, Salem; Yap, Tami; Bono, Johann S. de; Harrington, Kevin

doi:10.1016/s0959-8049(11)70870-x

Cited by 8 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, VACV has a proven track record of safety in people, as it was used to vaccinate against smallpox . Recently, a phase I clinical trial was completed at the Royal Marsden Hospital in London which demonstrated that intravenous administration of GL‐ONC1, clinical grade GLV‐1h68, was well tolerated by patients with no observed dose limiting toxicities …”

mentioning

confidence: 99%

Combination of fractionated irradiation with anti‐VEGF expressing vaccinia virus therapy enhances tumor control by simultaneous radiosensitization of tumor associated endothelium

Buckel

Advani

Frentzen

et al. 2013

Intl Journal of Cancer

View full text Add to dashboard Cite

Oncolytic viruses are currently in clinical trials for a variety of tumors, including high grade gliomas. A characteristic feature of high grade gliomas is their high vascularity and treatment approaches targeting tumor endothelium are under investigation, including bevacizumab. The aim of this study was to improve oncolytic viral therapy by combining it with ionizing radiation and to radiosensitize tumor vasculature through a viral encoded anti-angiogenic payload. Here, we show how vaccinia virusmediated expression of a single-chain antibody targeting VEGF resulted in radiosensitization of the tumor-associated vasculature. Cell culture experiments demonstrated that purified vaccinia virus encoded antibody targeting VEGF reversed VEGFinduced radioresistance specifically in endothelial cells but not tumor cells. In a subcutaneous model of U-87 glioma, systemically administered oncolytic vaccinia virus expressing anti-VEGF antibody (GLV-1h164) in combination with fractionated irradiation resulted in enhanced tumor growth inhibition when compared to nonanti-VEGF expressing oncolytic virus (GLV-1h68) and irradiation. Irradiation of tumor xenografts resulted in an increase in VACV replication of both GLV-1h68 and GLV-1h164. However, GLV-1h164 in combination with irradiation resulted in a drastic decrease in intratumoral VEGF levels and tumor vessel numbers in comparison to GLV-1h68 and irradiation. These findings demonstrate the incorporation of an oncolytic virus expressing an anti-VEGF antibody (GLV-1h164) into a fractionated radiation scheme to target tumor cells by enhanced VACV replication in irradiated tumors as well as to radiosensitize tumor endothelium which results in enhanced efficacy of combination therapy of human glioma xenografts.Glioblastoma multiforme (GBM) is the most aggressive form of malignant primary brain tumors. The overall prognosis for patients diagnosed with GBM continues to remain poor with a median overall survival of 12-14 months with current therapies. Treatment for GBM includes maximal surgical resection followed by concurrent temozolomide and radiotherapy but the deeply infiltrating nature of GBM often precludes complete surgical excision. 1 A defining histologic feature of GBM is their high vascularity. To improve the therapeutic efficacy of radiotherapy for GBM, preclinical

show abstract

mentioning

confidence: 99%

Combination of fractionated irradiation with anti‐VEGF expressing vaccinia virus therapy enhances tumor control by simultaneous radiosensitization of tumor associated endothelium

Buckel

Advani

Frentzen

et al. 2013

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Moreover, due to the absence of viral genome and the negative impact of oral bacteria on cell culture, plaque assay analysis was not performed. Human patients diagnosed with cancer receiving attenuated oncolytic VACV have been reported to develop mucocutaneous pustules a few days after treatment 9,12,14,[38][39][40][41] . In a few cases, PCR analysis con rmed that pustular lesions were induced by VACV 38,40 .…”

Section: Discussionmentioning

confidence: 99%

“…Mucocutaneous pustules have been reported after intratumoral or intravenous attenuated oncolytic VACV injections in patients with cancer 9,11,14,[38][39][40][41] . Environmental viral shedding is also a major issue as VACV can remain infectious for a long period in excreta [42][43][44] .…”

Section: Introductionmentioning

confidence: 99%

Safety, Biodistribution and Viral Shedding of Oncolytic Vaccinia Virus TG6002 Administered Intravenously in Healthy Beagle Dogs

Béguin

Gantzer

Farine

et al. 2020

Preprint

View full text Add to dashboard Cite

Oncolytic virotherapy is an emerging strategy that uses replication-competent viruses to kill tumor cells. We have previously reported the oncolytic effects of TG6002, a novel recombinant oncolytic vaccinia virus, in various preclinical human xenograft models and canine tumor explants. To assess the safety, biodistribution and shedding of TG6002 administered by the intravenous route, we conducted a study in four immune-competent healthy dogs. Three dogs each received a single intravenous injection of TG6002 at 1 x 105 PFU/kg, 1 x 106 PFU/kg or 1 x 107 PFU/kg, and one dog received three intravenous injections at 1 x 107 PFU/kg. The injections were well tolerated without any clinical, hematological or biochemical adverse events. Viral genomes were only detected in blood one hour after injection. Post mortem analyses allowed detection of viral DNA in the spleen of one dog. Viral genomes were not detected in the urine, saliva or feces of any dogs. Seven days after the injections, a dose-dependent immune response was identified. In conclusion, intravenous administration of TG6002 shows a good safety profile, a finding that supports the initiation of clinical trials in canine cancer patients as well as further development of TG6002 as a human cancer therapy.

show abstract

“…GLV-1h68 has been tested in a phase I clinical trial and is being tested in more phase I and II trials, demonstrating a safe profile and initial evidence of anti-tumor activity in cancer patients [34]. Previously, we have shown that treatment with GLV-1h68 resulted in tumor regression and reduced lymphatic metastases in mice bearing human prostate cancer PC3 xenografts [35].…”

Section: Discussionmentioning

confidence: 99%

Optical Detection and Virotherapy of Live Metastatic Tumor Cells in Body Fluids with Vaccinia Strains

et al. 2013

View full text Add to dashboard Cite

Metastatic tumor cells in body fluids are important targets for treatment, and critical surrogate markers for evaluating cancer prognosis and therapeutic response. Here we report, for the first time, that live metastatic tumor cells in blood samples from mice bearing human tumor xenografts and in blood and cerebrospinal fluid samples from patients with cancer were successfully detected using a tumor cell-specific recombinant vaccinia virus (VACV). In contrast to the FDA-approved CellSearch system, VACV detects circulating tumor cells (CTCs) in a cancer biomarker-independent manner, thus, free of any bias related to the use of antibodies, and can be potentially a universal system for detection of live CTCs of any tumor type, not limited to CTCs of epithelial origin. Furthermore, we demonstrate for the first time that VACV was effective in preventing and reducing circulating tumor cells in mice bearing human tumor xenografts. Importantly, a single intra-peritoneal delivery of VACV resulted in a dramatic decline in the number of tumor cells in the ascitic fluid from a patient with gastric cancer. Taken together, these results suggest VACV to be a useful tool for quantitative detection of live tumor cells in liquid biopsies as well as a potentially effective treatment for reducing or eliminating live tumor cells in body fluids of patients with metastatic disease.

show abstract

1258 POSTER Phase I Clinical Trial of a Genetically Modified Oncolytic Vaccinia Virus GL-ONC1 With Green Fluorescent Protein Imaging

Cited by 8 publications

References 0 publications

Combination of fractionated irradiation with anti‐VEGF expressing vaccinia virus therapy enhances tumor control by simultaneous radiosensitization of tumor associated endothelium

Combination of fractionated irradiation with anti‐VEGF expressing vaccinia virus therapy enhances tumor control by simultaneous radiosensitization of tumor associated endothelium

Safety, Biodistribution and Viral Shedding of Oncolytic Vaccinia Virus TG6002 Administered Intravenously in Healthy Beagle Dogs

Optical Detection and Virotherapy of Live Metastatic Tumor Cells in Body Fluids with Vaccinia Strains

Contact Info

Product

Resources

About