Immunotherapy in Glioblastoma: Current Approaches and Future Perspectives

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Jul 9

PMID 35806051

Authors

Ugur Sener

Michael W Ruff

Jian L Campian

Affiliations

Soon will be listed here.

Abstract

Glioblastoma (GBM) is the most common malignant brain tumor. Despite multimodality treatment with surgical resection, radiation therapy, chemotherapy, and tumor treating fields, recurrence is universal, median observed survival is low at 8 months and 5-year overall survival is poor at 7%. Immunotherapy aims to generate a tumor-specific immune response to selectively eliminate tumor cells. In treatment of GBM, immunotherapy approaches including use of checkpoint inhibitors, chimeric antigen receptor (CAR) T-Cell therapy, vaccine-based approaches, viral vector therapies, and cytokine-based treatment has been studied. While there have been no major breakthroughs to date and broad implementation of immunotherapy for GBM remains elusive, multiple studies are underway. In this review, we discuss immunotherapy approaches to GBM with an emphasis on molecularly informed approaches.

Citing Articles

Emerging nanoplatforms towards microenvironment-responsive glioma therapy.

Tripathy N, Sahoo L, Paikray S, Dilnawaz F Med Oncol. 2025; 42(2):46.

PMID: 39812745 DOI: 10.1007/s12032-024-02596-y.

Glioma immune microenvironment composition calculator (GIMiCC): a method of estimating the proportions of eighteen cell types from DNA methylation microarray data.

Pike S, Wiencke J, Zhang Z, Molinaro A, Hansen H, Koestler D Acta Neuropathol Commun. 2024; 12(1):170.

PMID: 39468647 PMC: 11514818. DOI: 10.1186/s40478-024-01874-0.

Review of Novel Surgical, Radiation, and Systemic Therapies and Clinical Trials in Glioblastoma.

Valerius A, Webb L, Thomsen A, Lehrer E, Breen W, Campian J Int J Mol Sci. 2024; 25(19).

PMID: 39408897 PMC: 11477105. DOI: 10.3390/ijms251910570.

-New frontiers in domain-inspired radiomics and radiogenomics: increasing role of molecular diagnostics in CNS tumor classification and grading following WHO CNS-5 updates.

Singh G, Singh A, Bae J, Manjila S, Spektor V, Prasanna P Cancer Imaging. 2024; 24(1):133.

PMID: 39375809 PMC: 11460168. DOI: 10.1186/s40644-024-00769-6.

Personalized mRNA vaccines in glioblastoma therapy: from rational design to clinical trials.

Karimi-Sani I, Molavi Z, Naderi S, Mirmajidi S, Zare I, Naeimzadeh Y J Nanobiotechnology. 2024; 22(1):601.

PMID: 39367418 PMC: 11453023. DOI: 10.1186/s12951-024-02882-x.

References

Sterner R, Sterner R . CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 2021; 11(4):69. PMC: 8024391. DOI: 10.1038/s41408-021-00459-7. View

Keskin D, Anandappa A, Sun J, Tirosh I, Mathewson N, Li S . Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial. Nature. 2018; 565(7738):234-239. PMC: 6546179. DOI: 10.1038/s41586-018-0792-9. View

Kim K, Gwak H, Han N, Hong E, Choi B, Lee S . Chimeric Antigen Receptor T Cells With Modified Interleukin-13 Preferentially Recognize IL13Rα2 and Suppress Malignant Glioma: A Preclinical Study. Front Immunol. 2021; 12:715000. PMC: 8606595. DOI: 10.3389/fimmu.2021.715000. View

Chiocca E, Nakashima H, Kasai K, Fernandez S, Oglesbee M . Preclinical Toxicology of rQNestin34.5v.2: An Oncolytic Herpes Virus with Transcriptional Regulation of the ICP34.5 Neurovirulence Gene. Mol Ther Methods Clin Dev. 2020; 17:871-893. PMC: 7195500. DOI: 10.1016/j.omtm.2020.03.028. View

Hryniewicki A, Wang C, Shatsky R, Coyne C . Management of Immune Checkpoint Inhibitor Toxicities: A Review and Clinical Guideline for Emergency Physicians. J Emerg Med. 2018; 55(4):489-502. DOI: 10.1016/j.jemermed.2018.07.005. View

Ardon H, Van Gool S, Verschuere T, Maes W, Fieuws S, Sciot R . Integration of autologous dendritic cell-based immunotherapy in the standard of care treatment for patients with newly diagnosed glioblastoma: results of the HGG-2006 phase I/II trial. Cancer Immunol Immunother. 2012; 61(11):2033-44. PMC: 11028710. DOI: 10.1007/s00262-012-1261-1. View

Cloughesy T, Landolfi J, Vogelbaum M, Ostertag D, Elder J, Bloomfield S . Durable complete responses in some recurrent high-grade glioma patients treated with Toca 511 + Toca FC. Neuro Oncol. 2018; 20(10):1383-1392. PMC: 6120351. DOI: 10.1093/neuonc/noy075. View

Desjardins A, Gromeier M, Herndon 2nd J, Beaubier N, Bolognesi D, Friedman A . Recurrent Glioblastoma Treated with Recombinant Poliovirus. N Engl J Med. 2018; 379(2):150-161. PMC: 6065102. DOI: 10.1056/NEJMoa1716435. View

Chongsathidkiet P, Jackson C, Koyama S, Loebel F, Cui X, Farber S . Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nat Med. 2018; 24(9):1459-1468. PMC: 6129206. DOI: 10.1038/s41591-018-0135-2. View

10.

Durrechou Q, Domblides C, Sionneau B, Lefort F, Quivy A, Ravaud A . Management of Immune Checkpoint Inhibitor Toxicities. Cancer Manag Res. 2020; 12:9139-9158. PMC: 7533913. DOI: 10.2147/CMAR.S218756. View

11.

Dono A, Zhu P, Holmes E, Takayasu T, Zhu J, Blanco A . Impacts of genotypic variants on survival following reoperation for recurrent glioblastoma. J Neurooncol. 2022; 156(2):353-363. PMC: 9338692. DOI: 10.1007/s11060-021-03917-1. View

12.

Omar N, Bentley R, Crossman D, Foote J, Koehler J, Markert J . Safety and interim survival data after intracranial administration of M032, a genetically engineered oncolytic HSV-1 expressing IL-12, in pet dogs with sporadic gliomas. Neurosurg Focus. 2021; 50(2):E5. PMC: 8383155. DOI: 10.3171/2020.11.FOCUS20844. View

13.

Wang D, Starr R, Chang W, Aguilar B, Alizadeh D, Wright S . Chlorotoxin-directed CAR T cells for specific and effective targeting of glioblastoma. Sci Transl Med. 2020; 12(533). PMC: 7500824. DOI: 10.1126/scitranslmed.aaw2672. View

14.

Patel D, Foreman P, Nabors L, Riley K, Gillespie G, Markert J . Design of a Phase I Clinical Trial to Evaluate M032, a Genetically Engineered HSV-1 Expressing IL-12, in Patients with Recurrent/Progressive Glioblastoma Multiforme, Anaplastic Astrocytoma, or Gliosarcoma. Hum Gene Ther Clin Dev. 2016; 27(2):69-78. PMC: 4932657. DOI: 10.1089/humc.2016.031. View

15.

Ahmed N, Brawley V, Hegde M, Bielamowicz K, Kalra M, Landi D . HER2-Specific Chimeric Antigen Receptor-Modified Virus-Specific T Cells for Progressive Glioblastoma: A Phase 1 Dose-Escalation Trial. JAMA Oncol. 2017; 3(8):1094-1101. PMC: 5747970. DOI: 10.1001/jamaoncol.2017.0184. View

16.

Beasley G, Nair S, Farrow N, Landa K, Selim M, Wiggs C . Phase I trial of intratumoral PVSRIPO in patients with unresectable, treatment-refractory melanoma. J Immunother Cancer. 2021; 9(4). PMC: 8057552. DOI: 10.1136/jitc-2020-002203. View

17.

Medawar P . Immunity to homologous grafted skin; the fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br J Exp Pathol. 1948; 29(1):58-69. PMC: 2073079. View

18.

Wilcox J, Ramakrishna R, Magge R . Immunotherapy in Glioblastoma. World Neurosurg. 2018; 116:518-528. DOI: 10.1016/j.wneu.2018.04.020. View

19.

Woroniecka K, Chongsathidkiet P, Rhodin K, Kemeny H, Dechant C, Farber S . T-Cell Exhaustion Signatures Vary with Tumor Type and Are Severe in Glioblastoma. Clin Cancer Res. 2018; 24(17):4175-4186. PMC: 6081269. DOI: 10.1158/1078-0432.CCR-17-1846. View

20.

Binder D, Ladomersky E, Lenzen A, Zhai L, Lauing K, Otto-Meyer S . Lessons learned from rindopepimut treatment in patients with EGFRvIII-expressing glioblastoma. Transl Cancer Res. 2018; 7(Suppl 4):S510-S513. PMC: 6166880. View