{"doi":"10.1158/1078-0432.c.6517752","title":"Data from Antiglioma Immunological Memory in Response to Conditional Cytotoxic/Immune-Stimulatory Gene Therapy: Humoral and Cellular Immunity Lead to Tumor Regression","abstract":"<div>Abstract<p><b>Purpose:</b> Glioblastoma multiforme is a deadly primary brain cancer. Because the tumor kills due to recurrences, we tested the hypothesis that a new treatment would lead to immunological memory in a rat model of recurrent glioblastoma multiforme.</p><p><b>Experimental Design:</b> We developed a combined treatment using an adenovirus (Ad) expressing <i>fms</i>-like tyrosine kinase-3 ligand (Flt3L), which induces the infiltration of immune cells into the tumor microenvironment, and an Ad expressing herpes simplex virus-1–thymidine kinase (TK), which kills proliferating tumor cells in the presence of ganciclovir.</p><p><b>Results:</b> This treatment induced immunological memory that led to rejection of a second glioblastoma multiforme implanted in the contralateral hemisphere and of an extracranial glioblastoma multiforme implanted intradermally. Rechallenged long-term survivors exhibited anti-glioblastoma multiforme–specific T cells and displayed specific delayed-type hypersensitivity. Using depleting antibodies, we showed that rejection of the second tumor was dependent on CD8<sup>+</sup> T cells. Circulating anti‐glioma antibodies were observed when glioblastoma multiforme cells were implanted intradermally in naïve rats or in long-term survivors. However, rats bearing intracranial glioblastoma multiforme only exhibited circulating antitumoral antibodies upon treatment with Ad-Flt3L + Ad-TK. This combined treatment induced tumor regression and release of the chromatin-binding protein high mobility group box 1 in two further intracranial glioblastoma multiforme models, that is, Fisher rats bearing intracranial 9L and F98 glioblastoma multiforme cells.</p><p><b>Conclusions:</b> Treatment with Ad-Flt3L + Ad-TK triggered systemic anti–glioblastoma multiforme cellular and humoral immune responses, and anti–glioblastoma multiforme immunological memory. Release of the chromatin-binding protein high mobility group box 1 could be used as a noninvasive biomarker of therapeutic efficacy for glioblastoma multiforme. The robust treatment efficacy lends further support to its implementation in a phase I clinical trial. (Clin Cancer Res 2009;15(19):6113–27)</p></div>","journal":null,"year":2023,"id":405114,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":394605,"name":"Marianela Candolfi","orcid":"0000-0002-0843-6568","position":1,"is_corresponding":false},{"id":425786,"name":"Gwendalyn D. King","orcid":"0000-0002-3659-9241","position":2,"is_corresponding":false},{"id":1183822,"name":"Kader Yagiz","orcid":null,"position":3,"is_corresponding":false},{"id":1112152,"name":"David Foulad","orcid":null,"position":4,"is_corresponding":false},{"id":1183421,"name":"Yohei Mineharu","orcid":"0000-0002-6346-3999","position":5,"is_corresponding":false},{"id":1183823,"name":"Kurt M. Kroeger","orcid":null,"position":6,"is_corresponding":false},{"id":1183824,"name":"Katherine A. Treuer","orcid":null,"position":7,"is_corresponding":false},{"id":1114039,"name":"W. Stephen Nichols","orcid":null,"position":8,"is_corresponding":false},{"id":1183422,"name":"Nicholas Sanderson","orcid":"0000-0003-1711-7275","position":9,"is_corresponding":false},{"id":992552,"name":"Jieping Yang","orcid":"0000-0002-0940-7662","position":10,"is_corresponding":false},{"id":1183825,"name":"Maksim Khayznikov","orcid":null,"position":11,"is_corresponding":false},{"id":608928,"name":"Nico van Rooijen","orcid":"0000-0002-6382-1813","position":12,"is_corresponding":false},{"id":236218,"name":"Pedro R. Löwenstein","orcid":"0000-0002-8427-4409","position":13,"is_corresponding":false},{"id":236219,"name":"María G. Castro","orcid":"0000-0003-2237-2756","position":14,"is_corresponding":false},{"id":238605,"name":"A.K.M. Ghulam Muhammad","orcid":null,"position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T01:20:49.237119Z","pmid":null,"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":[]}