Evolving CAR T-Cell Therapy to Overcome the Barriers in Treating Pediatric Central Nervous System Tumors.

Abstract

CNS tumors are the leading cause of cancer-related death in children, highlighting the dire need for new treatment strategies. CAR T cells represent a unique approach, distinct from the cytotoxic chemotherapies and small-molecule inhibitors that have dominated the clinical trial space for decades.

Phase I CAR T-cell trials have shown feasibility and possible efficacy against pediatric CNS tumors; however, many challenges must be overcome if these therapeutics are going to be beneficial to most affected children.

Although rapid translational development and early-phase trials have quickly evolved our understanding, the pediatric CNS CAR T-cell community now yearns for critical assessments and open dialogue about overcoming the remaining obstacles ahead.

COI Statement

CONFLICT OF INTEREST DISCLOSURE STATEMENT. N.A.V. holds equity in and serves as the Scientific Advisory Board Chair for BrainChild Bio, Inc. N.A.V. and J.B.F. are inventors on issued and pending patents related to CAR T cell therapies. L.D.W. serves on the Scientific Advisory Board of Autolomous, Ltd. All other authors declare no competing interests.

References:

Gardner RA, Finney O, Annesley C, Brakke H, Summers C, Leger K, et al. Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood 2017;129(25):3322–31 doi 10.1182/blood-2017-02-769208.
Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med 2018;378(5):439–48 doi 10.1056/NEJMoa1709866.
Mount CW, Majzner RG, Sundaresh S, Arnold EP, Kadapakkam M, Haile S, et al. Potent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M(+) diffuse midline gliomas. Nat Med 2018;24(5):572–9 doi 10.1038/s41591-018-0006-x.
Foster JB, Griffin C, Rokita JL, Stern A, Brimley C, Rathi K, et al. Development of GPC2-directed chimeric antigen receptors using mRNA for pediatric brain tumors. J Immunother Cancer 2022;10(9) doi 10.1136/jitc-2021-004450.
Ravanpay AC, Gust J, Johnson AJ, Rolczynski LS, Cecchini M, Chang CA, et al. EGFR806-CAR T cells selectively target a tumor-restricted EGFR epitope in glioblastoma. Oncotarget 2019;10(66):7080–95 doi 10.18632/oncotarget.27389.

Article info

Journal issue:

Volume: 15
Issue: 5

Doi:

10.1158/2159-8290.CD-24-1465

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Evolving CAR T-Cell Therapy to Overcome the Barriers in Treating Pediatric Central Nervous System Tumors.

Abstract

COI Statement

References:

Gardner RA, Finney O, Annesley C, Brakke H, Summers C, Leger K, et al. Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood 2017;129(25):3322–31 doi 10.1182/blood-2017-02-769208.
Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med 2018;378(5):439–48 doi 10.1056/NEJMoa1709866.
Mount CW, Majzner RG, Sundaresh S, Arnold EP, Kadapakkam M, Haile S, et al. Potent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M(+) diffuse midline gliomas. Nat Med 2018;24(5):572–9 doi 10.1038/s41591-018-0006-x.
Foster JB, Griffin C, Rokita JL, Stern A, Brimley C, Rathi K, et al. Development of GPC2-directed chimeric antigen receptors using mRNA for pediatric brain tumors. J Immunother Cancer 2022;10(9) doi 10.1136/jitc-2021-004450.
Ravanpay AC, Gust J, Johnson AJ, Rolczynski LS, Cecchini M, Chang CA, et al. EGFR806-CAR T cells selectively target a tumor-restricted EGFR epitope in glioblastoma. Oncotarget 2019;10(66):7080–95 doi 10.18632/oncotarget.27389.