{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:10:11Z","timestamp":1779149411512,"version":"3.51.4"},"reference-count":53,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T00:00:00Z","timestamp":1637107200000},"content-version":"vor","delay-in-days":56,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Association Fr\u00e9d\u00e9ric Fellay.","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"DOI":"10.13039\/501100009691","name":"Nuovo Soldati foundation for cancer research.","doi-asserted-by":"crossref","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/501100009691","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Basilea Pharmaceutica International Ltd.","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,22]]},"abstract":"<jats:p>Glioblastoma is a highly malignant brain tumor with no curative treatment options, and immune checkpoint blockade has not yet shown major impact. We hypothesized that drugs targeting mitosis might affect the tumor microenvironment and sensitize cancer cells to immunotherapy. We used 2 glioblastoma mouse models with different immunogenicity profiles, GL261 and SB28, to test the efficacy of antineoplastic and immunotherapy combinations. The spindle assembly checkpoint activator BAL101553 (lisavanbulin), agonistic anti-CD40 antibody, and double immune checkpoint blockade (anti\u2013programmed cell death 1 and anti\u2013cytotoxic T lymphocyte\u2013associated protein 4; anti\u2013PD-1 and anti\u2013CTLA-4) were evaluated individually or in combination for treating orthotopic GL261 and SB28 tumors. Genomic and immunological analyses were used to predict and interpret therapy responsiveness. BAL101553 monotherapy increased survival in immune checkpoint blockade\u2013resistant SB28 glioblastoma tumors and synergized with anti-CD40 antibody, in a T cell\u2013independent manner. In contrast, the more immunogenic and highly mutated GL261 model responded best to anti\u2013PD-1 and anti\u2013CTLA-4 therapy and more modestly to BAL101553 and anti-CD40 combination. Our results show that BAL101553 is a promising therapeutic agent for glioblastoma and could synergize with innate immune stimulation. Overall, these data strongly support immune profiling of glioblastoma patients and preclinical testing of combination therapies with appropriate models for particular patient groups.<\/jats:p>","DOI":"10.1172\/jci.insight.142980","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T12:03:35Z","timestamp":1629201815000},"source":"Crossref","is-referenced-by-count":14,"title":["Treating ICB-resistant glioma with anti-CD40 and mitotic spindle checkpoint controller BAL101553 (lisavanbulin)"],"prefix":"10.1172","volume":"6","author":[{"given":"Vassilis","family":"Genoud","sequence":"first","affiliation":[{"name":"Translational Research Center for Hemato-Oncology, Faculty of Medicine, University of Geneva, Geneva, Switzerland."},{"name":"Department of Oncology, University Hospitals of Geneva, Geneva, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7214-0307","authenticated-orcid":true,"given":"Felipe I.","family":"Espinoza","sequence":"additional","affiliation":[{"name":"Translational Research Center for Hemato-Oncology, Faculty of Medicine, University of Geneva, Geneva, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eliana","family":"Marinari","sequence":"additional","affiliation":[{"name":"Translational Research Center for Hemato-Oncology, Faculty of Medicine, University of Geneva, Geneva, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviane","family":"Rochemont","sequence":"additional","affiliation":[{"name":"Translational Research Center for Hemato-Oncology, Faculty of Medicine, University of Geneva, Geneva, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre-Yves","family":"Dietrich","sequence":"additional","affiliation":[{"name":"Translational Research Center for Hemato-Oncology, Faculty of Medicine, University of Geneva, Geneva, Switzerland."},{"name":"Department of Oncology, University Hospitals of Geneva, Geneva, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"McSheehy","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica International Ltd., Basel, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix","family":"Bachmann","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica International Ltd., Basel, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi A.","family":"Lane","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica International Ltd., Basel, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8999-6366","authenticated-orcid":true,"given":"Paul R.","family":"Walker","sequence":"additional","affiliation":[{"name":"Translational Research Center for Hemato-Oncology, Faculty of Medicine, University of Geneva, Geneva, Switzerland."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"232","published-online":{"date-parts":[[2021,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70025-7"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043330"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2016.25"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12030738"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2016.02.025"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1406498"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0491"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa4971"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-006-9265-3"},{"issue":"2","key":"B10","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.85841","article-title":"Glioblastoma-infiltrated innate immune cells resemble M0 macrophage phenotype","volume":"1","author":"Gabrusiewicz","year":"2016","journal-title":"JCI Insight"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3337"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-14-0215"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-0514"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-3573"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2018.1501137"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-18540-2"},{"key":"B17","doi-asserted-by":"crossref","unstructured":"Pohlmann J, et al. 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