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Targeted & Immune Therapies

Targeted therapies address specific features of glioblastoma, while immune therapies help the immune system attack tumour cells. Many approaches remain under clinical investigation.

Highlighted Papers

Chen, Z., Sinha, M., Nahm, J. et al. (2025):  CTNI-35. Survival Benefit of Adding Osimertinib to Standard Salvage Treatment Regimens for Recurrent Glioblastoma (GBM) with Epidermal Growth Factor Receptor (EGFR) Alterations, Neuro-Oncology, Volume 27, Issue Supplement_5, November 2025, Pages v133–v134, https://doi.org/10.1093/neuonc/noaf201.0531

In a retrospective study of 78 patients, osimertinib added to salvage therapy was associated with longer survival in EGFR-altered recurrent glioblastoma.

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Lai, S., Li, P., Liu, X., Liu, G. et al. (2024): Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase II trial. Cancer Biol Med. 2024 Mar 4;21(5):433–44. https://doi.org/10.20892/j.issn.2095-3941.2023.0373

In 33 patients, anlotinib plus Stupp therapy showed promising activity and manageable toxicity; the single-arm design cannot establish survival benefit.

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Choi et al., 2024 — “Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma”

This first-in-human study used CAR-T cells targeting EGFRvIII while releasing an engager molecule capable of redirecting T cells against wild-type EGFR. All three initial patients experienced rapid radiographic tumour regression, although the very small cohort and limited durability prevent conclusions about clinical efficacy.

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Wick, W., Gorlia, T., Bady, P., et al. (2016):  Phase II Study of Radiotherapy and Temsirolimus versus Radiochemotherapy with Temozolomide in Patients with Newly Diagnosed Glioblastoma without MGMT Promoter Hypermethylation (EORTC 26082). Clin Cancer Res. 2016 Oct 1;22(19):4797-4806. https://doi.org/10.1158/1078-0432.CCR-15-3153

Temsirolimus did not outperform temozolomide overall, but patients whose tumours had phosphorylated mTOR-Ser2448 showed a possible benefit.

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Nayak et al., 2021 — “Randomized Phase II and Biomarker Study of Pembrolizumab Plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma”

This randomised phase II study found that pembrolizumab was ineffective as monotherapy and provided limited benefit when combined with bevacizumab. The results illustrate the difficulty of achieving durable checkpoint-inhibitor responses in unselected glioblastoma patients.

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Ghannam et al., 2026 — “Tumor Transcriptional State Predicts Survival in Immune-Checkpoint-Blockade-Treated Glioblastoma”

This study identified tumour transcriptional states associated with survival following immune-checkpoint blockade. The findings could support biomarker-based patient selection but do not establish checkpoint inhibition as effective for all patients with glioblastoma.

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Further Literature

  • Campian, J. L., Le, S.B., Ghiaseddin, A. et al. (2026): Laser interstitial thermal therapy and adjuvant pembrolizumab in recurrent high-grade astrocytoma: a Phase 1/randomized Phase 2b trial. Nat Commun 17, 1763 (2026). https://doi.org/10.1038/s41467-026-69522-w

  • Abousaud, M., Faroqui, N. M., Lesser, G., et al. (2021): Clinical Experience using Osimertinib in Patients with Recurrent Malignant Gliomas Containing EGFR Alterations. J Cancer Sci Clin Ther. 2021;5(2):210-220. https://doi.org/10.26502/jcsct.5079114

  • Cardona, A. F., Jaramillo-Velásquez, D., Ruiz-Patiño, A. et al. (2021): Efficacy of osimertinib plus bevacizumab in glioblastoma patients with simultaneous EGFR amplification and EGFRvIII mutation. J Neurooncol 154, 353–364 (2021). https://doi.org/10.1007/s11060-021-03834-3

  • Chagoya, G., Kwatra, S. G., Nanni, C. W et al. (2020): Efficacy of osimertinib against EGFRvIII+ glioblastoma. Oncotarget. 2020 Jun 2;11(22):2074-2082. https://doi.org/10.18632/oncotarget.27599

  • Chen, Z., Sinha, M., Nahm, J. et al. (2025):  CTNI-35. Survival Benefit of Adding Osimertinib to Standard Salvage Treatment Regimens for Recurrent Glioblastoma (GBM) with Epidermal Growth Factor Receptor (EGFR) Alterations, Neuro-Oncology, Volume 27, Issue Supplement_5, November 2025, Pages v133–v134, https://doi.org/10.1093/neuonc/noaf201.0531

  • Cloughesy, T. F., Mochizuki, A. Y., Orpilla, J. R. et al. (2019): Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. Nat Med 25, 477–486 (2019). https://doi.org/10.1038/s41591-018-0337-7

  • Daei Sorkhabi, A., Sarkesh, A., Saeedi, H. et al. (2022): The Basis and Advances in Clinical Application of Cytomegalovirus-Specific Cytotoxic T Cell Immunotherapy for Glioblastoma Multiforme. Front Oncol. 2022 Apr 19;12:818447. https://doi.org/10.3389/fonc.2022.818447

  • Derby, S., Sweeting, l., Shad, S. . et al. (2025): OS04.7.A Results of The MGMT Methylated Substudy of Paradigm: a Phase I Study of Olaparib with Radiotherapy and Temozolomide in Elderly Patients with Newly Diagnosed Glioblastoma, Neuro-Oncology, Volume 27, Issue Supplement_3, October 2025, Page iii16, https://doi.org/10.1093/neuonc/noaf193.046

  • Duke University (2019):. Improved Anti-Tumor Immunotherapy Targeted Against Cytomegalovirus in Patients with Newly-Diagnosed WHO Grade IV Unmethylated Glioma (I-ATTAC). ClinicalTrials.gov: NCT03927222. Published April 25, 2019. Accessed August 22, 2026. https://clinicaltrials.gov/study/NCT03927222 and https://cdn.clinicaltrials.gov/large-docs/22/NCT03927222/Prot_SAP_001.pdf

  • El Ghalbouni, A., Snijders, T.J., Tolboom, N. et al. (2026): Near complete response recurrent glioblastoma after treatment with [131I]-Iodofalan. Eur J Nucl Med Mol Imaging 53, 4785–4787 (2026). https://doi.org/10.1007/s00259-025-07742-w

  • Ghannam, J.Y., Bryan, J., Weiss, J. et al. (2026): Tumor transcriptional state predicts survival in immune-checkpoint-blockade-treated glioblastoma. Nat Cancer 7, 964–982 (2026). https://doi.org/10.1038/s43018-026-01179-2

  • Giordano, F. A., Ganslandt, O., Münter, M. W. , et al. (2026): INTRAGO-II Study Group. Dose escalation with intraoperative radiotherapy in newly diagnosed glioblastoma (INTRAGO-II): an open-label, multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2026 Jul;27(7):864-878. https://doi.org/10.1016/S1470-2045(26)00235-4

  • Lai, S., Li, P., Liu, X., Liu, G. et al. (2024): Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase II trial. Cancer Biol Med. 2024 Mar 4;21(5):433–44. https://doi.org/10.20892/j.issn.2095-3941.2023.0373

  • Long, G. V., Shklovskaya, E., Satgunaseelan, L. et al. (2025): Neoadjuvant triplet immune checkpoint blockade in newly diagnosed glioblastoma. Nat Med 31, 1557–1566 (2025). https://doi.org/10.1038/s41591-025-03512-1

  • Lv, Y., Zhang J, Liu, F., Song, M., Hou, Y., Liang. N. (2019): Targeted therapy with anlotinib for patient with recurrent glioblastoma: A case report and literature review. Medicine (Baltimore). 2019 May;98(22):e15749. https://doi.org/10.1097/MD.0000000000015749

  • Nahm, J., Schumann, E. H., Vu, M. et al. (2023): BIOM-44. Improved Overall Survival of Recurrent Glioblastoma (GBM) Patients with EGFR amplification and EGFR VIII mutations treated with osimertinib: a retrospective review. Neuro Oncol. 2023 Nov 10;25(Suppl 5):v14. https://doi.org/10.1093/neuonc/noad179.0055

  • Nayak, L., Molinaro, A. M,, Peters, K. et al. (2021): Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma. Clin Cancer Res. 2021;27(4):1048-1057. https://doi.org/10.1158/1078-0432.CCR-20-2500

  • Pathak, A., Sravya, P., Colon, B. et al. (2026): GABA signaling activation drives glioblastoma progression in female mice through myeloid-derived suppressor cells. Nat Cancer 7, 1080–1093 (2026). https://doi.org/10.1038/s43018-026-01192-5

  • Pichler, J., Traub-Weidinger, T., Spiegl, K., Imamovic, L., Braat, A. J. A. T., Snijders, T. J., Verhoeff, J. J. C., Flamen, P., Tauchmanova, L., Hayward, C., Kluge, A. (2024): Results from a phase I study of 4-l-[131I]iodophenylalanine ([131I]IPA) with external radiation therapy in patients with recurrent glioblastoma (IPAX-1). Neuro-Oncology Advances, Volume 6, Issue 1, January-December 2024, vdae130, https://doi.org/10.1093/noajnl/vdae130

  • Reardon, D. A., Kim, T. M., Frenel, J. S., et al. (2021): Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE-028 trial. Cancer. 2021;127(10):1620-1629. https://doi.org/10.1002/cncr.33378

  • Surender, S., Haeusser, L. A., Kuhlburger, L et al. (2026): Molecular modulators of cyclin-dependent kinase 4/6 inhibitor response in experimental glioma identified through genome-wide CRISPR-Cas9 screening. Neuro Oncol. 2026 Aug 1;28(8):1904-1920. https://doi.org/10.1093/neuonc/noag093

  • Werlenius, K., Stragliotto, G., Strandeus, M. et al. (2021): A randomized phase II trial of efficacy and safety of the immunotherapy ALECSAT as an adjunct to radiotherapy and temozolomide for newly diagnosed glioblastoma. Neurooncol Adv. 2021 Oct 22;3(1):vdab156. https://doi.org/10.1093/noajnl/vdab156

  • Wick, W., Gorlia, T., Bady, P., et al. (2016):  Phase II Study of Radiotherapy and Temsirolimus versus Radiochemotherapy with Temozolomide in Patients with Newly Diagnosed Glioblastoma without MGMT Promoter Hypermethylation (EORTC 26082). Clin Cancer Res. 2016 Oct 1;22(19):4797-4806. https://doi.org/10.1158/1078-0432.CCR-15-3153

  • Woodworth, G., Anastasiadis, P., Ozair, A. et al. (2025): Microbubble-enhanced transcranial focused ultrasound with temozolomide for patients with high-grade glioma (BT008NA): a multicentre, open-label, phase 1/2 trial. The Lancet Oncology, 26, 1651-1664. https://doi.org/10.1016/S1470-2045(25)00492-9

  • Xu, Q. et al. (2022): A phase II study of anlotinib combined with temozolomide in the treatment of patients with recurrent glioblastoma.. J Clin Oncol 40, e14021-e14021(2022). https://doi.org/10.1200/JCO.2022.40.16_suppl.e14021

  • Zhai, K., Huang, Z., Huang, Q. et al. (2021): Pharmacological inhibition of BACE1 suppresses glioblastoma growth by stimulating macrophage phagocytosis of tumor cells. Nat Cancer 2, 1136–1151 (2021). https://doi.org/10.1038/s43018-021-00267-9

  • Personalized & Multimodal Immunotherapy

  • Garfinkle, E. A. R., Perales-Linares, R., Gimple, R. C. et al. (2026): Adjuvant personalized multivalent neoantigen DNA vaccination for MGMT unmethylated glioblastoma: a phase 1 trial. Nat Cancer 7, 1064–1079 (2026). https://doi.org/10.1038/s43018-026-01163-w

  • Kampers, L.F.C., Metselaar, D.S., Vinci, M., Scirocchi, F., Veldhuijzen van Zanten, S., Eyrich, M., Biassoni, V., Hulleman, E., Karremann, M., Stücker, W., et al. (2025): The Complexity of Malignant Glioma Treatment. Cancers 2025, 17, 879. https://doi.org/10.3390/cancers17050879

  • Kampers, L.F.C., Van de Vliet, P., Schirrmacher, V., W. Van Gool, S. W., Stücker, W. (2024):  From oncolytic virotherapy to individualized multimodal immunotherapy with focus on glioblastma. Reference Module in Biomedical Sciences, Elsevier, 2024. https://doi.org/10.1016/B978-0-443-14064-8.00020-5

  • Li, J., Chaurasiya, S., Sun, G. et al. (2026): Developing a multimodal therapy for glioblastoma using oncolytic virus delivering CD19 and EGFRvIII antigens and bi-specific CARs . Nat Commun 17, 4839 (2026). https://doi.org/10.1038/s41467-026-71021-x

  • Liu, Y., Zhou, F., Ali, H. et al. (2024): Immunotherapy for glioblastoma: current state, challenges, and future perspectives. Cell Mol Immunol 21, 1354–1375 (2024). https://doi.org/10.1038/s41423-024-01226-x

  • Pant, K., Glassy, M. C. Editorial (2025):: Current trends in immunotherapy: from monoclonal antibodies to CAR-T cells. Front Mol Med. 2025 Jun 2;5:1633469. https://doi.org/10.3389/fmmed.2025.1633469

  • Rieger, D., Becker, H., Walter, B. et al. (2025): Clinical outcome of biomarker-guided therapies in adult neuro-oncology patients: An update from the Tübingen molecular tumor board cohort. Neurooncol Adv. 2025 Feb 16;8(1):vdag031. http://doi.org/10.1093/noajnl/vdag031

  • Schirrmacher, V. Van Gool, S., Stuecker, W. (2024): Individualized Multimodal Immunotherapy (IMI): Scientific Rationale and Clinical Experience from a Single Institution. Biomedicines 2024, 12, 754. https://doi.org/10.3390/biomedicines12040754

  • Singh, D. D., Haque, S., Singh, A. K., Yadav, D. K. (2025): Advancing vaccine-based immunotherapy in glioblastoma treatment. Neurooncol Adv. 2025 Jun 24;7(1):vdaf135. https://doi.org/10.1093/noajnl/vdaf135

  • Tan, C. L., Lindner, K., Boschert, T. et al. (2025): Prediction of tumor-reactive T cell receptors from scRNA-seq data for personalized T cell therapy. Nat Biotechnol 43, 134–142 (2025). https://doi.org/10.1038/s41587-024-02161-y

  • Van de Vliet, P., Sprenger, T., Kampers, L.F.C., Makalowski, J., Schirrmacher, V., Stücker, W., Van Gool, S.W. (2023):  The Application of Evidence-Based Medicine in Individualized Medicine. Biomedicines 2023, 11, 1793. https://doi.org/10.3390/biomedicines11071793

  • Van Gool, S. Immunology FAQs, cancer immunotherapy explained. Video. https://www.youtube.com/watch?v=YAVR6ts4Mto, (accessed in 2026): 

  • Van Gool, S. Living with Glioblastoma, IOZK Treatment Options and Support. Webinar. https://www.youtube.com/watch?v=1Apmme_jX0I&t=28s. (accessed in 2026): 

  • Van Gool, S.W., Makalowski, J., Van de Vliet, P., Van Gool, S., Sprenger, T., Schirrmacher, V., Stuecker, W. (2023):  Individualized Multimodal Immunotherapy for Adults with IDH1 Wild-Type GBM: A Single Institute Experience. Cancers 2023, 15, 1194. https://doi.org/10.3390/cancers15041194

  • Zhou, Y., Shi, F., Zhu J, Yuan, Y., (2025):  An update on the clinical trial research of immunotherapy for glioblastoma. Front. Immunol., 2025 16:1582296. https://doi.org/10.3389/fimmu.2025.1582296

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