GL-ONC1

GL-ONC1 is an investigational therapeutic product consisting of the clinical grade formulation of the laboratory strain GLV-1h68, an oncolytic virus developed by Genelux Corporation.[1] GL-ONC1 is currently under evaluation in Phase I/II human clinical trials in the United States and Europe.[2]

GL-ONC1 is an attenuated vaccinia virus (Lister strain) that causes regression and elimination of a wide range of solid tumors in preclincal mouse models.[3] GLV-1h68 (GL-ONC1) was generated by insertion of three expression cassettes (encoding Renilla luciferase-Aequorea green fluorescent protein fusion, beta-galactosidase, and beta-glucuronidase) replacing the F14.5L, J2R (encoding thymidine kinase) and A56R (encoding hemagglutinin) loci of the parental viral Lister strain genome, respectively.[1] The oncolytic virus specifically infects and kills tumor cells which leads to oncolysis, which is thought to trigger an anti-tumor immune response.[4][5][6]

Clinical trials

Local Administration

One Phase I/II Study of intraperitoneal administration of GL-ONC1 in patients with advanced peritoneal carcinomatosis has been completed at the University of Tübingen.[7]

In a Phase I study at the Memorial Sloan Kettering Cancer Center intra-pleural administration of GL-ONC1 is evaluated in patients with malignant pleural effusion, which is caused by cancer from malignant pleural mesothelioma, non-small cell lung cancer (NSCLC), or breast cancer.[8] In this trial GL-ONC1 infection of tumor cells was identified in 6 out of 8 patients with epithelioid malignant pleural mesothelioma.[9]

Systemic Administration

Systemic administration of GL-ONC1 via intravenous injection is under investigation in two different clinical trials:

In one study at the Royal Marsden Hospital GL-ONC1 is administered to patients with advanced solid organ tumors as a monotherapy.[10] In another completed study at the Moores UC San Diego Cancer Center GL-ONC1 was given in combination with radiation therapy and cisplatin (CDDP) to patients with locoregionally advanced head and neck cancer.[11] Both studies showed that GL-ONC1 was well tolerated, and evidence of tumor colonization was observed.[12][13]

References

  1. 1 2 Zhang, Q; et al. (Oct 15, 2007). "Eradication of solid human breast tumors in nude mice with an intravenously injected light-emitting oncolytic vaccinia virus.". Cancer Research 67 (20): 10038–46. doi:10.1158/0008-5472.can-07-0146. PMID 17942938.
  2. ↑ "Search of: GL-ONC1 - List Results - ClinicalTrials.gov". clinicaltrials.gov.
  3. ↑ pubmeddev. "GLV-1h68 - PubMed - NCBI". nih.gov.
  4. ↑ Melcher, A; et al. (Apr 19, 2011). "Thunder and lightning: immunotherapy and oncolytic viruses collide.". Molecular Therapy 19 (6): 1008–16. doi:10.1038/mt.2011.65. PMC 3129809. PMID 21505424.
  5. ↑ Tong, AW; et al. (2012). "Oncolytic Viruses for Induction of Anti-Tumor Immunity". Current Pharmaceutical Biotechnology 13 (9): 1750–60. doi:10.2174/138920112800958913. PMID 21740355.
  6. ↑ Naik, JD; et al. (2011). "Immune Recruitment and Therapeutic Synergy: Keys to Optimizing Oncolytic Viral Therapy?". Clinical Cancer Research 17 (13): 4214–24. doi:10.1158/1078-0432.ccr-10-2848. PMC 3131422. PMID 21576084.
  7. ↑ "A Study of GL-ONC1, an Oncolytic Vaccinia Virus, in Patients With Advanced Peritoneal Carcinomatosis". clinicaltrials.gov.
  8. ↑ "Intra-pleural Administration of GL-ONC1, a Genetically Modified Vaccinia Virus, in Patients With Malignant Pleural Effusion: Primary, Metastases and Mesothelioma". clinicaltrials.gov.
  9. ↑ "http://abstracts.asco.org/156/AbstView_156_148847.html". asco.org. External link in |title= (help)
  10. ↑ "Safety Study of GL-ONC1, an Oncolytic Virus, in Patients With Advanced Solid Tumors". clinicaltrials.gov.
  11. ↑ "Safety Study of Attenuated Vaccinia Virus (GL-ONC1)With Combination Therapy in Head & Neck Cancer". clinicaltrials.gov.
  12. ↑ "Phase I clinical trial of a genetically modified and oncolytic vaccinia virus GL-ONC1 with green fluorescent protein imaging. - 2012 ASCO Annual Meeting - Abstracts - Meeting Library". asco.org.
  13. ↑ "http://abstracts.asco.org/156/AbstView_156_143293.html". asco.org. External link in |title= (help)

External links

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