{"doi":"10.1172/jci141614","title":"Immunostimulatory bacterial antigen–armed oncolytic measles virotherapy significantly increases the potency of anti-PD1 checkpoint therapy","abstract":"Clinical immunotherapy approaches are lacking efficacy in the treatment of glioblastoma (GBM). In this study, we sought to reverse local and systemic GBM-induced immunosuppression using the Helicobacter pylori neutrophil-activating protein (NAP), a potent TLR2 agonist, as an immunostimulatory transgene expressed in an oncolytic measles virus (MV) platform, retargeted to allow viral entry through the urokinase-type plasminogen activator receptor (uPAR). While single-agent murine anti-PD1 treatment or repeat in situ immunization with MV-s-NAP-uPA provided modest survival benefit in MV-resistant syngeneic GBM models, the combination treatment led to synergy with a cure rate of 80% in mice bearing intracranial GL261 tumors and 72% in mice with CT-2A tumors. Combination NAP-immunovirotherapy induced massive influx of lymphoid cells in mouse brain, with CD8+ T cell predominance; therapeutic efficacy was CD8+ T cell dependent. Inhibition of the IFN response pathway using the JAK1/JAK2 inhibitor ruxolitinib decreased PD-L1 expression on myeloid-derived suppressor cells in the brain and further potentiated the therapeutic effect of MV-s-NAP-uPA and anti-PD1. Our findings support the notion that MV strains armed with bacterial immunostimulatory antigens represent an effective strategy to overcome the limited efficacy of immune checkpoint inhibitor-based therapies in GBM, creating a promising translational strategy for this lethal brain tumor.","journal":"Journal of Clinical Investigation","year":2021,"id":154684,"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":62,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"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":248201,"name":"Cheyne Kurokawa","orcid":null,"position":1,"is_corresponding":false},{"id":656116,"name":"Kimberly Viker","orcid":null,"position":2,"is_corresponding":false},{"id":655288,"name":"Arun Ammayappan","orcid":"0000-0002-0453-7310","position":3,"is_corresponding":false},{"id":273498,"name":"S. Keith Anderson","orcid":"0000-0003-1542-9726","position":4,"is_corresponding":false},{"id":655289,"name":"Sotiris Sotiriou","orcid":"0000-0002-6060-4995","position":5,"is_corresponding":false},{"id":655290,"name":"Kyriakos Chatzopoulos","orcid":"0000-0001-6769-6952","position":6,"is_corresponding":false},{"id":256583,"name":"Katayoun Ayasoufi","orcid":"0000-0002-3797-0823","position":7,"is_corresponding":false},{"id":256585,"name":"Aaron J. Johnson","orcid":"0000-0002-7921-484X","position":8,"is_corresponding":false},{"id":656117,"name":"Ianko Iankov","orcid":null,"position":9,"is_corresponding":false},{"id":247463,"name":"Evanthia Galanis","orcid":"0000-0001-8014-786X","position":10,"is_corresponding":false},{"id":655287,"name":"Eleni Panagioti","orcid":"0000-0002-7574-1378","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-18T23:43:54.469024Z","pmid":"34196308","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":[]}