{"doi":"10.1016/j.omton.2024.200761","title":"Oncolytic herpes simplex viruses designed for targeted treatment of EGFR-bearing tumors","abstract":"Oncolytic herpes simplex viruses (oHSVs) have emerged as leading cancer therapeutic agents. Effective oHSV virotherapy may ultimately require both intratumoral and systemic vector administration to target the primary tumor and distant metastases. An attractive approach to enhancing oHSV tumor specificity is engineering the virus envelope glycoproteins for selective recognition of and infection via tumor-specific cell surface proteins. We previously demonstrated that oHSV could be retargeted to EGFR-expressing cells by incorporation of a single chain antibody (scFv) at the N-terminus of glycoprotein D (gD). Here we compared retargeted oHSV generated by insertion of scFv, affibody molecule, or VHH antibody ligands at different positions within the N-terminus of gD. When compared to the scFv-directed oHSV, VHH and affibody molecules mediated enhanced EGFR-specific tumor cell entry, spread and cell killing in vitro, and enabled long-term tumor-specific virus replication following intravenous delivery in vivo. Moreover, oHSV retargeted via a VHH ligand reduced tumor growth upon intravenous injection and achieved complete tumor destruction after intratumoral injection. Systemic oHSV delivery is important for treatment of metastatic disease, and our enhancements in targeted oHSV design are a critical step in creating an effective tumor-specific oHSV for safe administration via the bloodstream.","journal":"Molecular Therapy Oncology","year":2024,"id":453992,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9533,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":394963,"name":"Bonnie L. Hall","orcid":"0000-0002-7431-0349","position":1,"is_corresponding":false},{"id":394964,"name":"Justus B. Cohen","orcid":"0000-0003-1208-1883","position":2,"is_corresponding":false},{"id":318201,"name":"Joseph C. Glorioso","orcid":"0000-0002-1818-2645","position":3,"is_corresponding":false},{"id":1277250,"name":"Selene Ingusci","orcid":"0000-0002-8534-5942","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T02:03:07.923686Z","pmid":"38596286","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":[]}