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Is Immunotherapy the Future of Glioblastoma Treatment?
Samantha DiGrande
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Is Immunotherapy the Future of Glioblastoma Treatment?

Samantha DiGrande
Immunotherapy has seen great success in the treatment of numerous cancers, from melanoma to lung, breast, colorectal, kidney, and even some brain cancers. But thus far, despite several attempts, the devastating brain disease glioblastoma has not been among the immunotherapy success stories. In fact, glioblastoma researchers have had few advances in more than a decade.
The vaccine DCVax-L is currently being tested in a phase 3 trial involving patients with glioblastoma whose tumors could be removed surgically. It uses dendritic cells (a type of immune cell) that are engineered to provoke an immune response against multiple proteins, or antigens, on tumors.20

Additionally, researchers are looking at oncolytic virus therapy as a potential treatment for glioblastoma. Originally, these viruses were developed as therapies to directly infect and kill cancer cells; however, investigators now believe that these viruses work similarly to vaccines and are able to stimulate an immune response against tumors.

“I think that there has been a lot of active, ongoing research, and the fact that we make breakthroughs in other cancers makes us more resolute in our drive and hopes to find help for patients with glioblastoma, and finding a cure,” said Lim.

Mary Caffrey contributed to this report.

REFERENCES:
  1. Immunotherapy by cancer type. Cancer Research Institute website. cancerresearch.org/immunotherapy/cancer-types. Accessed January 31, 2019.
  2. NCI Staff. Can immunotherapy succeed in glioblastoma? National Cancer Institute website. cancer.gov/news-events/cancer-cur- rents-blog/2018/immunotherapy-glioblastoma. Published May 24, 2018. Updated June 6, 2018. Accessed January 28, 2019.
  3. Harder BG, Blomquist MR, Wang J, et al. Developments in blood– brain barrier penetrance and drug repurposing for improved treatment of glioblastoma. Front Oncol. 2018;8:462. doi: 10.3389/fonc.2018.00462.
  4. An investigational immuno-therapy study of nivolumab compared to temozolomide, each given with radiation therapy, for newly-diagnosed patients with glioblastoma (GBM, a malignant brain cancer) (CheckMate 498). clinicaltrials.gov/ct2/show/NCT02617589. Updated January 15, 2019. Accessed February 7, 2019.
  5. An investigational immuno-therapy study of temozolomide plus radiation therapy with nivolumab or placebo, for newly diagnosed patients with glioblastoma (GBM, a malignant brain cancer) (Check- Mate 548). clinicaltrials.gov/ct2/show/NCT02667587. Updated January 15, 2019. Accessed February 7, 2019.
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  7. Reardon DA, Wucherpfennig KW, Freeman G, et al. An update of vaccine therapy and other immunotherapeutic approaches for glioblastoma. Expert Rev Vaccines. 2013;12(6):597-615. doi: 10.1586/ erv.13.41.
  8. Glioblastoma (GBM). American Brain Tumor Association website. abta.org/tumor_types/glioblastoma-gbm/. Accessed February 4, 2019.
  9. Tamimi AF, Juweid M. Epidemiology and outcome of glioblastoma. In: De Vleeschouwer S, ed. Glioblastoma [Internet]. Brisbane, Australia: Codon Publications; 2017:chapter 8. ncbi.nlm.nih.gov/ books/NBK470003/. Accessed February 7, 2019. doi: 10.15586/ codon.glioblastoma.2017.ch8.
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  11. Ducharme J. John McCain and Edward Kennedy died of the same cancer, exactly 9 years apart. Time website. time.com/5378429/ john-mccain-edward-kennedy-glioblastoma/. Published August 26, 2018. Accessed January 28, 2019.
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  13. Our mission. Biden Cancer Initiative website. bidencancer.org. Accessed January 28, 2019.
  14. Bagley SJ, Desai AS, Linette GP, June CH, O’Rourke DM. CAR T-cell therapy for glioblastoma: recent clinical advances and future challenges. Neuro Oncol. 2018;20(11):1429-1438. doi: 10.1093/ neuonc/noy032.
  15. O’Rourke DM, Nasrallah MP, Desai A, et al. A single dose of peripher- ally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma.Sci Transl Med. 2017;9(399):eaaa0984. doi: 10.1126/scitranslmed. aaa0984.
  16. Reardon DA, Kaley TJ, Dietrich J, et al. Phase 2 study to evaluate the safety and efficacy of MEDI4736 (durvalumab [DUR]) in glioblasto- ma (GBM) patients: an update. J Clin Oncol. 2017;35(15 suppl):abstr 2042. doi: 10.1200/JCO.2017.35.15_suppl.2042.
  17. Woroniecka K, Chongsathidkiet P, Rhodin K, et al. T-cell exhaustion signatures vary with tumor type and are severe in glioblastoma.Clin Cancer Res. 2018;24(17):4175-4186. doi: 10.1158/1078-0432. CCR-17-1846.
  18. Louveau A, Smirnov I, Keyes TJ, et al. Structural and function features of central nervous system lymphatic vessels. Nature. 2015;523(7560):337-341. doi: 10.1038/nature14432.
  19. Filley AC, Henriquez M, Dey M. Recurrent glioma clinical trial, CheckMate-143: the game is not over yet. Oncotarget. 2017;8(53):91779-91794. doi: 10.18632/oncotarget.21586.
  20. Liau L, Ashkan K, Tran DD, et al. First results on survival from a large phase 3 clinical trial of an autologous dendritic cell vaccine in newly diagnosed glioblastoma [published correction appears in J Transl Med. 2018;16(1):179]. J Transl Med. 2018;16(1):142. doi: 10.1186/ s12967-018-1507-6.
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