GL-ONC1 (USAN: olvimulogene nanivacirepvec; abbreviated as Olvi-Vec) is an investigational therapeutic product consisting of the clinical grade formulation of the laboratory strain GLV-1h68, an

oncolytic virus An oncolytic virus is a virus that preferentially infects and kills cancer cells. As the infected cancer cells are destroyed by lysis#Oncolysis, oncolysis, they release new infectious virus particles or virus, virions to help destroy the remaining ...

developed by Genelux Corporation. GL-ONC1 is currently under evaluation in Phase I/II human clinical trials in the United States and Europe. GL-ONC1 (CAS Registry Number (CAS RN): 1473430-36-2) is a triple modified and attenuated

vaccinia virus ''Vaccinia virus'' (VACV or VV) is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, which encodes approximately 250 genes. The dimensions of the ...

(Lister strain) that causes regression and elimination of a wide range of solid tumors in preclinical mouse models. It was generated by insertion of three expression cassettes (encoding

Renilla ''Renilla'' is a genus of sea pen. It is the only genus within the monotypic family Renillidae. Species The following species are recognized: * ''Renilla amethystina'' Verrill, 1864 * '' Renilla koellikeri'' Pfeffer, 1886 * ''Renilla muelleri' ...

luciferase Luciferase is a generic term for the class of oxidative enzymes that produce bioluminescence, and is usually distinguished from a photoprotein. The name was first used by Raphaël Dubois who invented the words ''luciferin'' and ''luciferase'', ...

- Aequorea

green fluorescent protein The green fluorescent protein (GFP) is a protein that exhibits bright green fluorescence when exposed to light in the blue to ultraviolet range. The label ''GFP'' traditionally refers to the protein first isolated from the jellyfish ''Aequorea ...

fusion,

beta-galactosidase β-Galactosidase (EC 3.2.1.23, lactase, beta-gal or β-gal; systematic name β-D-galactoside galactohydrolase), is a glycoside hydrolase enzyme that catalyzes hydrolysis of terminal non-reducing β-D-galactose residues in β-D-galactosides. β- ...

, and

beta-glucuronidase Beta-glucuronidases are members of the glycosidase family of enzymes that catalyze breakdown of complex carbohydrates. Human β-glucuronidase is a type of glucuronidase (a member of glycosidase Family 2) that catalyzes hydrolysis of β-D-glucur ...

) into the F14.5L, J2R (encoding thymidine kinase) and A56R (encoding hemagglutinin) loci of the parental viral Lister strain genome, respectively. The oncolytic virus specifically infects and kills tumor cells which leads to oncolysis, immune activation and triggering anti-tumor immune responses.

Clinical trials

Regional (cavity) administration

One Phase I/II Study of

intraperitoneal The peritoneum is the serous membrane forming the lining of the abdominal cavity or coelom in amniotes and some invertebrates, such as annelids. It covers most of the intra-abdominal (or coelomic) organs, and is composed of a layer of mesotheli ...

administration of GL-ONC1 in patients with advanced

peritoneal carcinomatosis Peritoneal carcinomatosis (PC) is intraperitoneal dissemination (carcinosis) of any form of cancer that does not originate from the peritoneum itself. PC is most commonly seen in abdominopelvic malignancies. Computed tomography (CT) is particula ...

has been completed. A Phase II study of

administration of GL-ONC1 (Olvi-Vec) in heavily-pretreated patients with platinum-resistant/refractory ovarian cancer was completed. Positive clinical data have been reported in IGCS 2020 and ESMO 2020 conferences. A registration trial of Olvi-Vec(aka GL-ONC1)-primed immunochemotherapy is being planned. In a Phase I study, intra-pleural administration of GL-ONC1 is being evaluated in patients with

malignant pleural effusion Malignant pleural effusion is a condition in which cancer causes an abnormal amount of fluid to collect between the thin layers of tissue (pleura) lining the outside of the lung and the wall of the chest cavity. Lung cancer and breast cancer accoun ...

, which is caused by cancer from malignant pleural

mesothelioma Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium). The most common area affected is the lining of the lungs and chest wall. Less commonly the lining ...

non-small cell lung cancer Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to sm ...

(NSCLC), or

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...

. In this trial GL-ONC1 infection of tumor cells was identified in 6 out of 8 patients with epithelioid malignant pleural mesothelioma.

Systemic (intravenous) administration

Systemic administration of GL-ONC1 via intravenous injection was under investigation in multiple clinical trials: In one study, GL-ONC1 was administered to patients with advanced solid organ tumors as a monotherapy. In another completed study, GL-ONC1 was given in combination with radiation therapy and cisplatin (CDDP) to patients with locoregionally advanced head and neck cancer. Mell LK et al. (July 2017)

References

{{Reflist

External links

Genelux website
Experimental cancer treatments Virotherapy Oncolytic virus