{"doi":"10.1016/j.ymthe.2021.02.001","title":"Oncolytic Viruses for Systemic Administration: Engineering a Whole Different Animal","abstract":"Unimpeded progression of metastatic cancer is the principal cause of mortality in cancer patients. It occurs when every and all therapeutic options have been exhausted, necessitating an urgent search for novel therapies to slow cancer progression and educate the immune system to find and eliminate disseminated cancer cells. A promising approach to control disseminated cancer involves the administration of oncolytic virus, a novel cancer treatment modality that has proven efficacious at suppressing tumor growth in numerous pre-clinical models and in cancer patients with localized disease. To date, two oncolytic virus drugs have been approved for clinical use: Oncorine H101, an oncolytic adenovirus approved for treating patients with nasopharyngeal carcinoma by the Chinese Food and Drug Administration,1Liang M. Oncorine, the World First Oncolytic Virus Medicine and its Update in China.Curr. Cancer Drug Targets. 2018; 18: 171-176Crossref PubMed Scopus (67) Google Scholar and Imlygic, an oncolytic herpes simplex virus-1-based drug, approved for treating advanced melanoma by the US Food and Drug Administration.2Pol J. Kroemer G. Galluzzi L. First oncolytic virus approved for melanoma immunotherapy.OncoImmunology. 2015; 5: e1115641Crossref PubMed Scopus (165) Google Scholar In both cases, therapeutic efficacy is observed upon injecting oncolytic viruses directly into tumors. Clinical trials have shown that, although direct intra-tumoral injection of Imlygic is well tolerated and suppresses the growth of local melanoma lesions, distant visceral metastases remain largely refractory to Imlygic.3Andtbacka R.H. Ross M. Puzanov I. Milhem M. Collichio F. Delman K.A. Amatruda T. Zager J.S. Cranmer L. Hsueh E. et al.Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial.Ann. Surg. Oncol. 2016; 23: 4169-4177Crossref PubMed Scopus (170) Google Scholar Two principal and complementary approaches are currently being explored to improve the efficacy of local virotherapy against disseminated disease. These include “arming” oncolytic viruses with immune-stimulatory transgenes and combining intra-tumoral virus administration with immune-checkpoint inhibitors4Senior M. Checkpoint inhibitors go viral.Nat. Biotechnol. 2019; 37: 12-17Crossref PubMed Scopus (17) Google Scholar to stimulate the so-called abscopal effect, whereby distant metastatic lesions undergo regression due to virus-mediated activation of systemic anti-tumor immunity. While both of these approaches improved systemic anti-tumor response after local administration of oncolytic viruses,5Ribas A. Dummer R. Puzanov I. VanderWalde A. Andtbacka R.H.I. Michielin O. et al.Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy.Cell. 2017; 170: 1109-1119.e10Abstract Full Text Full Text PDF PubMed Scopus (708) Google Scholar the observation that tumor lesions subjected to direct virus injection typically undergo strongest regression (compared to non-injected distant metastatic nodules)3Andtbacka R.H. Ross M. Puzanov I. Milhem M. Collichio F. Delman K.A. Amatruda T. Zager J.S. Cranmer L. Hsueh E. et al.Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial.Ann. Surg. Oncol. 2016; 23: 4169-4177Crossref PubMed Scopus (170) Google Scholar suggests that systemic administration of therapeutic viruses (allowing virus access to all tumor lesions in the body) may be the most efficacious approach to controlling disseminated metastatic disease. The unique advantage of oncolytic viruses as cancer therapeutics is that, unlike small molecule or antibody-based drugs, they represent a therapeutic platform that can be iteratively tailored for specific application though targeted engineering of their structural and regulatory elements, thus endowing them with ever-improved properties to reduce side effe","journal":"Molecular Therapy","year":2021,"id":175120,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":290772,"name":"Dmitry M. Shayakhmetov","orcid":"0000-0002-8320-9007","position":1,"is_corresponding":false},{"id":290768,"name":"Svetlana Atasheva","orcid":"0000-0002-7816-393X","position":0,"is_corresponding":true}],"reference_count":15,"raw_metadata":null,"created_at":"2026-07-18T23:47:11.249697Z","pmid":"33577782","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}