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Review
. 2022 Jan;22(1):1-10.
doi: 10.1007/s11910-022-01176-9. Epub 2022 Feb 2.

Advances in Immunotherapies for Gliomas

Michael Zhang  1 , John Choi  1 , Michael Lim  2   3
Affiliations
Review

Advances in Immunotherapies for Gliomas

Michael Zhang et al. Curr Neurol Neurosci Rep. 2022 Jan.

Abstract

Purpose of review: Immunotherapy-based treatment of glioblastoma has been challenging because of the tumor's limited neoantigen profile and weakly immunogenic composition. This article summarizes the current clinical trials underway by evaluating the leading immunotherapy paradigms, the encountered barriers, and the future directions needed to overcome such tumor evasion.

Recent findings: A limited number of phase III trials have been completed for checkpoint inhibitor, vaccine, as well as gene therapies, and have been unable to show improvement in survival outcomes. Nevertheless, these trials have also shown these strategies to be safe and promising with further adaptations. Further large-scale studies for chimeric antigen receptors T cell therapies and viral therapies are anticipated. Many current trials are broadening the number of antigens targeted and modulating the microtumor environment to abrogate early mechanisms of resistance. Future GBM treatment will also likely require synergistic effects by combination regimens.

Keywords: Checkpoint inhibitors; Gene therapy; Glioblastoma; Immunotherapy; Vaccines, Viral therapy.

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Conflict of interest statement

Conflict of Interest Michael Zhang (Funding by the National Institutes of Health (5T32CA009695-27). Michael Lim (Funding from Arbor Pharmaceuticals, Accuray, BMS, Novartis, Biohaven; consultant: BMS, Merck, SQZ Biotechnologies, Tocagen, VBI, Biohaven; patents: combining focused radiation and immunotherapy, combining local chemotherapy and immunotherapy).

References

    1. Stupp R, Weber DC. The role of radio- and chemotherapy in glioblastoma. Onkologie. 2005;28(6–7):315–7. - PubMed

    1. Chongsathidkiet P, Jackson C, Koyama S, Loebel F, Cui X, Farber SH, et al. Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nat Med. 2018;24(9):1459–68.

      • Murine and human study demonstrating that T cell lymphopenia is accompanied by naïve T cell accumulation in bone marrow, attributed to S1P1 on the T cell surface.

    1. Jackson CM, Choi J, Lim M. Mechanisms of immunotherapy resistance: lessons from glioblastoma. Nat Immunol. 2019;20(9):1100–9. - PubMed
    1. Gandhi L, Garassino MC. Pembrolizumab plus chemotherapy in lung cancer. N Engl J Med. 2018;379(11):e18. - PubMed
    1. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2019;381(16):1535–46. - PubMed

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