rRp450

rRp450 is an oncolytic herpes simplex virus (oHSV) mutant under development as an anticancer therapeutic. It is a genetically modified version of HSV-1 KOS strain that has been engineered with specific properties to target cancer cells.\n\nThe virus is ICP6-deleted (missing the UL39 gene that encodes the large subunit of ribonucleotide reductase), which makes it selectively replicate in rapidly dividing cells like cancer cells while sparing normal cells[1][2]. In place of the deleted UL39 gene, rRp450 expresses rat CYP2B1, a cytochrome P450 enzyme that can activate prodrugs like cyclophosphamide (CPA)[2][4].\n\nThis dual mechanism allows rRp450 to kill tumor cells through direct viral lysis while also enhancing the antitumor effect of cyclophosphamide when used in combination therapy[2][4]. Studies have shown that cyclophosphamide can in turn enhance viral replication in vivo by counteracting the host immune response against the virus[2].\n\n## Development Status and Clinical Trials\n\nrRp450 was initially developed by the National Cancer Institute and has reached Phase 1 clinical trials[1]. There is a Phase I trial studying the side effects and best dose of rRp450 in treating patients with primary liver cancer or cancer that has spread to the liver[9]. The purpose of this research study is to determine the safety of rRp450 and the highest dose that can be given to people safely[3].\n\n## Efficacy and Safety Profile\n\nPreclinical studies have demonstrated that rRp450 is approximately 10,000-fold attenuated in replication compared to wild-type HSV-1 in human primary hepatocytes, differentiated primary foreskin keratinocytes, and primary Schwann cells[2]. This significant attenuation contributes to its safety profile.\n\nIn animal models, rRp450 has shown efficacy against various tumor types:\n- In a human xenograft sarcoma model, cyclophosphamide enhanced the antitumor efficacy of rRp450[2]\n- In orthotopic models of brain tumors like medulloblastoma and atypical teratoid/rhabdoid tumors (AT/RT), rRp450 significantly improved survival, with some animals becoming tumor-free at the experiment endpoint[4]\n\nSafety studies in immunocompetent mice have shown that both intravenous and intracranial administration of rRp450 at doses of 10^8 plaque-forming units, alone or followed by cyclophosphamide, were well tolerated with no significant effects on blood counts or chemistries[2].\n\n## Therapeutic Areas\n\nThe primary therapeutic areas being investigated for rRp450 include:\n- Neoplasms (cancer)[1]\n- Digestive system diseases, particularly liver tumors and liver metastases[1][3][9]\n- Brain tumors, including medulloblastoma and atypical teratoid/rhabdoid tumors (AT/RT)[4]

Other names

oncolytic HSV-1 rRp450