Clinical trials that are currently underway for OVs in GB

OVTrial numberPhasesAnti-tumor effects
Vaccinia virus TG6002NCT03294486Recruiting; I/IIThe removal of the TK gene relies on actively dividing cells to supply TK for replication. Incorporating GM-CSF is intended to strengthen the immune response against the tumor. Introducing the FCU1 gene, along with the prodrug 5-FC, inhibits tumor growth.
Reovirus Reolysin

  • NCT00528684

  • NCT02444546

  • Completed; I

  • Active; not recruiting; I

Tropism targets tumor cells with increased RAS expression. The inclusion of GM-CSF aims to enhance the immune response against the tumor.
Herpesvirus C134 M032 G207 rQNestin

  • NCT03657576

  • NCT02062827

  • NCT00028158

  • NCT03152318

  • Active; not recruiting; I

  • Recruiting; I

  • Completed; I/II

  • Recruiting; I

In HSV lacking the TK gene, replication relies heavily on actively dividing cells to provide the necessary TK. HSV with a deletion in the γ34.5 gene and a mutation in UL39 uses enzymes from actively dividing tumor cells for replication. Additionally, HSV expressing IL-12 exhibits anti-tumor effects in vivo by combining oncolysis with the stimulation of T cell-mediated immune responses.
Parvovirus H1 H-1PVNCT01301430Completed; I/IIReplication takes place in actively dividing cells during the S-phase. The antitumor effect results from a combination of oncolytic effects and immune responses.
Retrovirus Toca 511NCT01470794Completed; IDecrease in tumor size, and suppression of tumor growth through the delivery of therapeutic genes.
PVS-RIPO

  • NCT03043391

  • NCT04479241

  • NCT01491893

  • NCT02986178

  • Recruiting; I

  • Recruiting; II

The OVs demonstrate a preference for tumor cells that express high levels of the CD155. By replacing the IRES sequence with HRV2, the virus reduces neurotoxicity and improves its ability to destroy tumors.
Measles virus MV-CEANCT0039029Completed; IThe OV targets tumor cells with high CD46 receptor levels, destroying them and triggering an immune response against the tumor.
Adenovirus DNX2401 DNX2240 CRAd-S-pk7

  • NCT01956734

  • NCT03714334

  • NCT03072134

  • NCT03896568

  • Recruiting; II

  • Completed; I

  • Completed; I

  • Recruiting; I

Adenovirus containing mutations in E1B and E1A selectively targets abnormalities in the p53 or Rb pathways of tumor cells. It redirects GB cells with low coxsackievirus and adenovirus receptor expression by modifying them with RGD or EGFR. The in vivo anti-tumor effect is mainly due to oncolysis and changes in the GB microenvironment influenced by T cells and macrophages.
HSV-1 MVR-C5252 (C5252)NCT05095441Not yet recruiting; IC5252 induces a potent antitumor immune response and works synergistically with traditional cancer therapies to enhance their anticancer effects. Additionally, it exhibits anti-angiogenic properties.
HSV-1 M032NCT02062827Recruiting; IThis OV kills tumor cells directly through its replication process and then spreads to nearby tumor cells, continuing the destruction. It also serves as a gene therapy vector, causing tumor cells to produce and release the immunity-stimulating protein IL-12. This promotes an immune response against tumor cells, enhancing the therapy’s antitumor effect. Additionally, IL-12 has an antiangiogenic effect, further contributing to the treatment’s efficacy.

5-FC: 5-fluorocytosine; CD155: polio-rhinovirus receptor; CD46: cluster of differentiation 46; EGFR: epidermal growth factor receptor; FCU1: flucytosine converting enzyme 1; GB: glioblastoma; GM-CSF: granulocyte-macrophage colony-stimulating factor; HRV2: human rhinovirus 2; HSV: herpes simplex virus; HSV-1: herpes simplex virus type 1; IL-12: interleukin-12; IRES: internal ribosome entry site; MV-CEA: measles virus encoding carcinoembryonic antigen; OVs: oncolytic viruses; p53: protein 53; PVS-RIPO: recombinant nonpathogenic polio-rhinovirus; RAS: rat sarcoma; Rb: retinoblastoma protein; RGD: Arg-Gly-Asp peptide; TK: thymidine kinase; Toca 511: vocimagene amiretrorepvec