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Oncology

Insight into the Progress in CAR-T Cell Therapy and Combination with Other Therapies for Glioblastoma

, ORCID Icon, , &
Pages 4121-4141 | Received 26 Apr 2023, Accepted 02 Aug 2023, Published online: 11 Sep 2023

References

  • Shen SH, Woroniecka K, Barbour AB, Fecci PE, Sanchez-Perez L, Sampson JH. CAR T cells and checkpoint inhibition for the treatment of glioblastoma. Expert Opin Biol Ther. 2020;20(6):579–591. doi:10.1080/14712598.2020.1727436
  • Le N, Do DT, Chiu FY, Yapp E, Yeh HY, Chen CY. XGBoost improves classification of MGMT promoter methylation status in IDH1 wildtype glioblastoma. J Pers Med. 2020;10(3):128.
  • Bagley SJ, Kothari S, Rahman R, et al. Glioblastoma clinical trials: current landscape and opportunities for improvement. Clin Cancer Res. 2022;28(4):594–602. doi:10.1158/1078-0432.CCR-21-2750
  • Fisher JP, Adamson DC. Current FDA-approved therapies for high-grade malignant gliomas. Biomedicines. 2021;9(3):324. doi:10.3390/biomedicines9030324
  • Stupp R, Taillibert S, Kanner A, et al. Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA. 2017;318(23):2306–2316. doi:10.1001/jama.2017.18718
  • Bausart M, Préat V, Malfanti A. Immunotherapy for glioblastoma: the promise of combination strategies. J Exp Clin Cancer Res. 2022;41(1):35. doi:10.1186/s13046-022-02251-2
  • Medikonda R, Dunn G, Rahman M, Fecci P, Lim M. A review of glioblastoma immunotherapy. J Neurooncol. 2021;151(1):41–53. doi:10.1007/s11060-020-03448-1
  • Huang B, Li X, Li Y, Zhang J, Zong Z, Zhang H. Current immunotherapies for glioblastoma multiforme. Front Immunol. 2020;11:603911. doi:10.3389/fimmu.2020.603911
  • Bikfalvi A, da Costa CA, Avril T, et al. Challenges in glioblastoma research: focus on the tumor microenvironment. Trends Cancer. 2023;9(1):9–27. doi:10.1016/j.trecan.2022.09.005
  • Wang Z, Wang Y, Chang M, et al. Single-cell transcriptomic analyses provide insights into the cellular origins and drivers of brain metastasis from lung adenocarcinoma. Neuro Oncol. 2023;25(7):1262–1274. doi:10.1093/neuonc/noad017
  • Grabowski MM, Sankey EW, Ryan KJ, et al. Immune suppression in gliomas. J Neurooncol. 2021;151(1):3–12. doi:10.1007/s11060-020-03483-y
  • Nixon BG, Kuo F, Ji L, et al. Tumor-associated macrophages expressing the transcription factor IRF8 promote T cell exhaustion in cancer. Immunity. 2022;55(11):2044–2058.e5. doi:10.1016/j.immuni.2022.10.002
  • Lee E, Yong RL, Paddison P, Zhu J. Comparison of glioblastoma (GBM) molecular classification methods. Semin Cancer Biol. 2018;53:201–211. doi:10.1016/j.semcancer.2018.07.006
  • Ma Q, Long W, Xing C, et al. Cancer stem cells and immunosuppressive microenvironment in glioma. Front Immunol. 2018;9:2924. doi:10.3389/fimmu.2018.02924
  • Rodriguez S, Staicu GA, Sevastre AS, et al. Glioblastoma stem cells-useful tools in the battle against cancer. Int J Mol Sci. 2022;23(9):4602. doi:10.3390/ijms23094602
  • Dotti G, Gottschalk S, Savoldo B, Brenner MK. Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol Rev. 2014;257(1):107–126. doi:10.1111/imr.12131
  • Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 2021;11(4):69. doi:10.1038/s41408-021-00459-7
  • Sabbagh A, Beccaria K, Ling X, et al. Opening of the blood-brain barrier using low-intensity pulsed ultrasound enhances responses to immunotherapy in preclinical glioma models. Clin Cancer Res. 2021;27(15):4325–4337. doi:10.1158/1078-0432.CCR-20-3760
  • Choi BD, Yu X, Castano AP, et al. CRISPR-Cas9 disruption of PD-1 enhances activity of universal EGFRvIII CAR T cells in a preclinical model of human glioblastoma. J Immunother Cancer. 2019;7(1):304. doi:10.1186/s40425-019-0806-7
  • Asmamaw Dejenie T, Tiruneh G/Medhin M, Dessie Terefe G, Tadele Admasu F, Wale Tesega W, Chekol Abebe E. Current updates on generations, approvals, and clinical trials of CAR T-cell therapy. Hum Vaccin Immunother. 2022;18(6):2114254. doi:10.1080/21645515.2022.2114254
  • Chen L, Chen F, Li J, et al. CAR-T cell therapy for lung cancer: potential and perspective. Thorac Cancer. 2022;13(7):889–899. doi:10.1111/1759-7714.14375
  • Dunn GP, Cloughesy TF, Maus MV, Prins RM, Reardon DA, Sonabend AM. Emerging immunotherapies for malignant glioma: from immunogenomics to cell therapy. Neuro Oncol. 2020;22(10):1425–1438. doi:10.1093/neuonc/noaa154
  • Tudor T, Binder ZA, O’Rourke DM. CAR T Cells. Neurosurg Clin N Am. 2021;32(2):249–263. doi:10.1016/j.nec.2020.12.005
  • Gieryng A, Pszczolkowska D, Walentynowicz KA, Rajan WD, Kaminska B. Immune microenvironment of gliomas. Lab Invest. 2017;97(5):498–518. doi:10.1038/labinvest.2017.19
  • Spill F, Reynolds DS, Kamm RD, Zaman MH. Impact of the physical microenvironment on tumor progression and metastasis. Curr Opin Biotechnol. 2016;40:41–48. doi:10.1016/j.copbio.2016.02.007
  • 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
  • Rafiq S, Hackett CS, Brentjens RJ. Engineering strategies to overcome the current roadblocks in CAR T cell therapy. Nat Rev Clin Oncol. 2020;17(3):147–167. doi:10.1038/s41571-019-0297-y
  • Singer LS, Feldman AZ, Buerki RA, Horbinski CM, Lukas RV, Stupp R. The impact of the molecular classification of glioblastoma on the interpretation of therapeutic clinical trial results. Chin Clin Oncol. 2021;10(4):38. doi:10.21037/cco-21-33
  • Śledzińska P, Bebyn M, Szczerba E, et al. Glioma 2021 WHO classification: the superiority of NGS over IHC in routine diagnostics. Mol Diagn Ther. 2022;26(6):699–713. doi:10.1007/s40291-022-00612-3
  • Stichel D, Ebrahimi A, Reuss D, et al. Distribution of EGFR amplification, combined chromosome 7 gain and chromosome 10 loss, and TERT promoter mutation in brain tumors and their potential for the reclassification of IDHwt astrocytoma to glioblastoma. Acta Neuropathol. 2018;136(5):793–803. doi:10.1007/s00401-018-1905-0
  • Verhaak RG, Hoadley KA, Purdom E, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17(1):98–110. doi:10.1016/j.ccr.2009.12.020
  • Wang Q, Hu B, Hu X, et al. Tumor evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment. Cancer Cell. 2017;32(1):42–56.e6. doi:10.1016/j.ccell.2017.06.003
  • Le N, Hung T, Do DT, Lam L, Dang LH, Huynh TT. Radiomics-based machine learning model for efficiently classifying transcriptome subtypes in glioblastoma patients from MRI. Comput Biol Med. 2021;132:104320. doi:10.1016/j.compbiomed.2021.104320
  • Du L, Lee JH, Jiang H, et al. β-Catenin induces transcriptional expression of PD-L1 to promote glioblastoma immune evasion. J Exp Med. 2020;217(11):e20191115. doi:10.1084/jem.20191115
  • Rutledge WC, Kong J, Gao J, et al. Tumor-infiltrating lymphocytes in glioblastoma are associated with specific genomic alterations and related to transcriptional class. Clin Cancer Res. 2013;19(18):4951–4960. doi:10.1158/1078-0432.CCR-13-0551
  • Hu C, Wang K, Damon C, et al. ATRX loss promotes immunosuppressive mechanisms in IDH1 mutant glioma. Neuro Oncol. 2022;24(6):888–900. doi:10.1093/neuonc/noab292
  • Choi SI, Yin J. Prospective approaches to enhancing CAR T cell therapy for glioblastoma. Front Immunol. 2022;13:1008751. doi:10.3389/fimmu.2022.1008751
  • Bailey SR, Maus MV. Gene editing for immune cell therapies. Nat Biotechnol. 2019;37(12):1425–1434. doi:10.1038/s41587-019-0137-8
  • Chailyan A, Marcatili P, Tramontano A. The association of heavy and light chain variable domains in antibodies: implications for antigen specificity. FEBS J. 2011;278(16):2858–2866. doi:10.1111/j.1742-4658.2011.08207.x
  • Brown CE, Alizadeh D, Starr R, et al. Regression of glioblastoma after chimeric antigen receptor T-cell therapy. N Engl J Med. 2016;375(26):2561–2569. doi:10.1056/NEJMoa1610497
  • Lee L, Draper B, Chaplin N, et al. An April-based chimeric antigen receptor for dual targeting of BCMA and TACI in multiple myeloma. Blood. 2018;131(7):746–758. doi:10.1182/blood-2017-05-781351
  • Alabanza L, Pegues M, Geldres C, et al. Function of novel anti-CD19 chimeric antigen receptors with human variable regions is affected by hinge and transmembrane domains. Mol Ther. 2017;25(11):2452–2465. doi:10.1016/j.ymthe.2017.07.013
  • James SE, Greenberg PD, Jensen MC, et al. Antigen sensitivity of CD22-specific chimeric TCR is modulated by target epitope distance from the cell membrane. J Immunol. 2008;180(10):7028–7038. doi:10.4049/jimmunol.180.10.7028
  • Bridgeman JS, Hawkins RE, Bagley S, Blaylock M, Holland M, Gilham DE. The optimal antigen response of chimeric antigen receptors harboring the CD3zeta transmembrane domain is dependent upon incorporation of the receptor into the endogenous TCR/CD3 complex. J Immunol. 2010;184(12):6938–6949. doi:10.4049/jimmunol.0901766
  • Guedan S, Posey AD Jr, Shaw C, et al. Enhancing CAR T cell persistence through ICOS and 4-1BB costimulation. JCI Insight. 2018;3(1). doi:10.1172/jci.insight.96976
  • Maher J, Brentjens RJ, Gunset G, Rivière I, Sadelain M. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta /CD28 receptor. Nat Biotechnol. 2002;20(1):70–75. doi:10.1038/nbt0102-70
  • O’Rourke DM, Nasrallah MP, Desai A, et al. A single dose of peripherally infused EGFRvIII-directed CAR T cells mediates antigen loss and induces adaptive resistance in patients with recurrent glioblastoma. Sci Transl Med. 2017;9(399). doi:10.1126/scitranslmed.aaa0984
  • Goff SL, Morgan RA, Yang JC, et al. Pilot trial of adoptive transfer of chimeric antigen receptor-transduced T cells targeting EGFRvIII in patients with glioblastoma. J Immunother. 2019;42(4):126–135. doi:10.1097/CJI.0000000000000260
  • Brown CE, Badie B, Barish ME, et al. Bioactivity and safety of IL13Rα2-redirected chimeric antigen receptor CD8+ T cells in patients with recurrent glioblastoma. Clin Cancer Res. 2015;21(18):4062–4072. doi:10.1158/1078-0432.CCR-15-0428
  • Ahmed N, Brawley V, Hegde M, et al. 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. doi:10.1001/jamaoncol.2017.0184
  • Majzner RG, Ramakrishna S, Yeom KW, et al. GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas. Nature. 2022;603(7903):934–941. doi:10.1038/s41586-022-04489-4
  • Lin Q, Ba T, Ho J, et al. First-in-human trial of EphA2-redirected CAR T-cells in patients with recurrent glioblastoma: a preliminary report of three cases at the starting dose. Front Oncol. 2021;11:694941. doi:10.3389/fonc.2021.694941
  • Jang JK, Pyo J, Suh CH, Park HS, Chae YK, Kim KW. Safety and efficacy of chimeric antigen receptor T-cell therapy for glioblastoma: a systemic review and meta-analysis. Front Oncol. 2022;12:851877. doi:10.3389/fonc.2022.851877
  • Feldman L, Brown C, Badie B. Chimeric Antigen Receptor (CAR) T cell therapy for glioblastoma. Neuromolecular Med. 2022;24(1):35–40. doi:10.1007/s12017-021-08689-5
  • Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124(2):188–195. doi:10.1182/blood-2014-05-552729
  • Morgan RA, Yang JC, Kitano M, Dudley ME, Laurencot CM, Rosenberg SA. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol Ther. 2010;18(4):843–851. doi:10.1038/mt.2010.24
  • Karschnia P, Teske N, Thon N, et al. Chimeric antigen receptor T cells for glioblastoma: current concepts, challenges, and future perspectives. Neurology. 2021;97(5):218–230. doi:10.1212/WNL.0000000000012193
  • Brammer JE, Braunstein Z, Katapadi A, et al. Early toxicity and clinical outcomes after chimeric antigen receptor T-cell (CAR-T) therapy for lymphoma. J Immunother Cancer. 2021;9(8):e002303. doi:10.1136/jitc-2020-002303
  • Rubin DB, Danish HH, Ali AB, et al. Neurological toxicities associated with chimeric antigen receptor T-cell therapy. Brain. 2019;142(5):1334–1348. doi:10.1093/brain/awz053
  • Brown CE, Aguilar B, Starr R, et al. Optimization of IL13Rα2-targeted chimeric antigen receptor T cells for improved anti-tumor efficacy against glioblastoma. Mol Ther. 2018;26(1):31–44. doi:10.1016/j.ymthe.2017.10.002
  • Shergalis A, Bankhead A 3rd, Luesakul U, Muangsin N, Neamati N, Barker EL. Current challenges and opportunities in treating glioblastoma. Pharmacol Rev. 2018;70(3):412–445. doi:10.1124/pr.117.014944
  • Lanitis E, Irving M, Coukos G. Targeting the tumor vasculature to enhance T cell activity. Curr Opin Immunol. 2015;33:55–63. doi:10.1016/j.coi.2015.01.011
  • Palazón A, Aragonés J, Morales-Kastresana A, de Landázuri MO, Melero I. Molecular pathways: hypoxia response in immune cells fighting or promoting cancer. Clin Cancer Res. 2012;18(5):1207–1213. doi:10.1158/1078-0432.CCR-11-1591
  • Zhang D, Li AM, Hu G, et al. PHGDH-mediated endothelial metabolism drives glioblastoma resistance to chimeric antigen receptor T cell immunotherapy. Cell Metab. 2023;35(3):517–534.e8. doi:10.1016/j.cmet.2023.01.010
  • Sackstein R, Schatton T, Barthel SR. T-lymphocyte homing: an underappreciated yet critical hurdle for successful cancer immunotherapy. Lab Invest. 2017;97(6):669–697. doi:10.1038/labinvest.2017.25
  • Wang G, Zhang Z, Zhong K, et al. CXCL11-armed oncolytic adenoviruses enhance CAR-T cell therapeutic efficacy and reprogram tumor microenvironment in glioblastoma. Mol Ther. 2023;31(1):134–153. doi:10.1016/j.ymthe.2022.08.021
  • Harlin H, Meng Y, Peterson AC, et al. Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment. Cancer Res. 2009;69(7):3077–3085. doi:10.1158/0008-5472.CAN-08-2281
  • Andersson A, Yang SC, Huang M, et al. IL-7 promotes CXCR3 ligand-dependent T cell antitumor reactivity in lung cancer. J Immunol. 2009;182(11):6951–6958. doi:10.4049/jimmunol.0803340
  • Mlecnik B, Tosolini M, Charoentong P, et al. Biomolecular network reconstruction identifies T-cell homing factors associated with survival in colorectal cancer. Gastroenterology. 2010;138(4):1429–1440. doi:10.1053/j.gastro.2009.10.057
  • Jin L, Tao H, Karachi A, et al. CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors. Nat Commun. 2019;10(1):4016. doi:10.1038/s41467-019-11869-4
  • Salmon H, Remark R, Gnjatic S, Merad M. Host tissue determinants of tumour immunity. Nat Rev Cancer. 2019;19(4):215–227. doi:10.1038/s41568-019-0125-9
  • Zhao B, Xia Y, Yang F, et al. Molecular landscape of IDH-mutant astrocytoma and oligodendroglioma grade 2 indicate tumor purity as an underlying genomic factor. Mol Med. 2022;28(1):34. doi:10.1186/s10020-022-00454-z
  • Kato D, Yaguchi T, Iwata T, et al. Prospects for personalized combination immunotherapy for solid tumors based on adoptive cell therapies and immune checkpoint blockade therapies. Nihon Rinsho Meneki Gakkai Kaishi. 2017;40(1):68–77. doi:10.2177/jsci.40.68
  • Mohme M, Schliffke S, Maire CL, et al. Immunophenotyping of newly diagnosed and recurrent glioblastoma defines distinct immune exhaustion profiles in peripheral and tumor-infiltrating lymphocytes. Clin Cancer Res. 2018;24(17):4187–4200. doi:10.1158/1078-0432.CCR-17-2617
  • Zhu H, You Y, Shen Z, Shi L. EGFRvIII-CAR-T cells with PD-1 knockout have improved anti-glioma activity. Pathol Oncol Res. 2020;26(4):2135–2141. doi:10.1007/s12253-019-00759-1
  • Wang Z, Wang Z, Zhang C, et al. Genetic and clinical characterization of B7-H3 (CD276) expression and epigenetic regulation in diffuse brain glioma. Cancer Sci. 2018;109(9):2697–2705. doi:10.1111/cas.13744
  • An Z, Aksoy O, Zheng T, Fan QW, Weiss WA. Epidermal growth factor receptor and EGFRvIII in glioblastoma: signaling pathways and targeted therapies. Oncogene. 2018;37(12):1561–1575. doi:10.1038/s41388-017-0045-7
  • Vora P, Venugopal C, Salim SK, et al. The rational development of CD133-targeting immunotherapies for glioblastoma. Cell Stem Cell. 2020;26(6):832–844.e6. doi:10.1016/j.stem.2020.04.008
  • Yang YN, Zhang XH, Wang YM, Zhang X, Gu Z. miR-204 reverses temozolomide resistance and inhibits cancer initiating cells phenotypes by degrading FAP-α in glioblastoma. Oncol Lett. 2018;15(5):7563–7570. doi:10.3892/ol.2018.8301
  • Liu K, Jiang L, Shi Y, et al. Hypoxia-induced GLT8D1 promotes glioma stem cell maintenance by inhibiting CD133 degradation through N-linked glycosylation. Cell Death Differ. 2022;29(9):1834–1849. doi:10.1038/s41418-022-00969-2
  • Sangsuwannukul T, Supimon K, Sujjitjoon J, et al. Anti-tumour effect of the fourth-generation chimeric antigen receptor T cells targeting CD133 against cholangiocarcinoma cells. Int Immunopharmacol. 2020;89(Pt B):107069. doi:10.1016/j.intimp.2020.107069
  • Dai H, Tong C, Shi D, et al. Efficacy and biomarker analysis of CD133-directed CAR T cells in advanced hepatocellular carcinoma: a single-arm, open-label, phase II trial. Oncoimmunology. 2020;9(1):1846926. doi:10.1080/2162402X.2020.1846926
  • Zhu X, Prasad S, Gaedicke S, Hettich M, Firat E, Niedermann G. Patient-derived glioblastoma stem cells are killed by CD133-specific CAR T cells but induce the T cell aging marker CD57. Oncotarget. 2015;6(1):171–184. doi:10.18632/oncotarget.2767
  • Zhang C, Zhang Z, Li F, et al. Large-scale analysis reveals the specific clinical and immune features of B7-H3 in glioma. Oncoimmunology. 2018;7(11):e1461304. doi:10.1080/2162402X.2018.1461304
  • Tang X, Zhao S, Zhang Y, et al. B7-H3 as a novel CAR-T therapeutic target for glioblastoma. Mol Ther Oncolytics. 2019;14:279–287. doi:10.1016/j.omto.2019.07.002
  • Vitanza NA, Wilson AL, Huang W, et al. Intraventricular B7-H3 CAR T cells for diffuse intrinsic pontine glioma: preliminary first-in-human bioactivity and safety. Cancer Discov. 2022;13(1):114–131.
  • Chaudhry K, Geiger A, Dowlati E, et al. Co-transducing B7H3 CAR-NK cells with the DNR preserves their cytolytic function against GBM in the presence of exogenous TGF-β. Mol Ther Methods Clin Dev. 2022;27:415–430. doi:10.1016/j.omtm.2022.10.010
  • DeBin JA, Maggio JE, Strichartz GR. Purification and characterization of chlorotoxin, a chloride channel ligand from the venom of the scorpion. Am J Physiol. 1993;264(2 Pt 1):C361–C369. doi:10.1152/ajpcell.1993.264.2.C361
  • Soroceanu L, Gillespie Y, Khazaeli MB, Sontheimer H. Use of chlorotoxin for targeting of primary brain tumors. Cancer Res. 1998;58(21):4871–4879.
  • Wang D, Starr R, Chang WC, et al. Chlorotoxin-directed CAR T cells for specific and effective targeting of glioblastoma. Sci Transl Med. 2020;12(533). doi:10.1126/scitranslmed.aaw2672
  • Dardevet L, Rani D, Aziz TA, et al. Chlorotoxin: a helpful natural scorpion peptide to diagnose glioma and fight tumor invasion. Toxins. 2015;7(4):1079–1101. doi:10.3390/toxins7041079
  • Nausch N, Cerwenka A. NKG2D ligands in tumor immunity. Oncogene. 2008;27(45):5944–5958. doi:10.1038/onc.2008.272
  • Yang D, Sun B, Dai H, et al. T cells expressing NKG2D chimeric antigen receptors efficiently eliminate glioblastoma and cancer stem cells. J Immunother Cancer. 2019;7(1):171. doi:10.1186/s40425-019-0642-9
  • Zhang P, Zhang Y, Ji N. Challenges in the treatment of glioblastoma by chimeric antigen receptor T-cell immunotherapy and possible solutions. Front Immunol. 2022;13:927132. doi:10.3389/fimmu.2022.927132
  • Hegde M, Mukherjee M, Grada Z, et al. Tandem CAR T cells targeting HER2 and IL13Rα2 mitigate tumor antigen escape. J Clin Invest. 2016;126(8):3036–3052. doi:10.1172/JCI83416
  • Yin Y, Rodriguez JL, Li N, et al. Locally secreted BiTEs complement CAR T cells by enhancing killing of antigen heterogeneous solid tumors. Mol Ther. 2022;30(7):2537–2553. doi:10.1016/j.ymthe.2022.05.011
  • Choi BD, Yu X, Castano AP, et al. CAR-T cells secreting BiTEs circumvent antigen escape without detectable toxicity. Nat Biotechnol. 2019;37(9):1049–1058. doi:10.1038/s41587-019-0192-1
  • Bielamowicz K, Fousek K, Byrd TT, et al. Trivalent CAR T cells overcome interpatient antigenic variability in glioblastoma. Neuro Oncol. 2018;20(4):506–518. doi:10.1093/neuonc/nox182
  • Choe JH, Watchmaker PB, Simic MS, et al. SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma. Sci Transl Med. 2021;13(591). doi:10.1126/scitranslmed.abe7378
  • Sabahi M, Jabbari P, Alizadeh Haghighi M, et al. Proposing a tandem AND-gate CAR T cell targeting glioblastoma multiforme. Med Hypotheses. 2020;137:109559. doi:10.1016/j.mehy.2020.109559
  • Johnson A, Townsend M, O’Neill K. Tumor microenvironment immunosuppression: a roadblock to CAR T-cell advancement in solid tumors. Cells. 2022;11(22):3626.
  • Chmielewski M, Abken H. TRUCKs: the fourth generation of CARs. Expert Opin Biol Ther. 2015;15(8):1145–1154. doi:10.1517/14712598.2015.1046430
  • Agliardi G, Liuzzi AR, Hotblack A, et al. Intratumoral IL-12 delivery empowers CAR-T cell immunotherapy in a pre-clinical model of glioblastoma. Nat Commun. 2021;12(1):444. doi:10.1038/s41467-020-20599-x
  • Lai J, Mardiana S, House IG, et al. Adoptive cellular therapy with T cells expressing the dendritic cell growth factor Flt3L drives epitope spreading and antitumor immunity. Nat Immunol. 2020;21(8):914–926. doi:10.1038/s41590-020-0676-7
  • Feins S, Kong W, Williams EF, Milone MC, Fraietta JA. An introduction to chimeric antigen receptor (CAR) T-cell immunotherapy for human cancer. Am J Hematol. 2019;94(S1):S3–S9. doi:10.1002/ajh.25418
  • Neelapu SS, Tummala S, Kebriaei P, et al. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15(1):47–62. doi:10.1038/nrclinonc.2017.148
  • Singh N, Barrett DM, Grupp SA. Roadblocks to success for RNA CARs in solid tumors. Oncoimmunology. 2014;3(12):e962974. doi:10.4161/21624011.2014.962974
  • Morgan RA, Chinnasamy N, Abate-Daga D, et al. Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy. J Immunother. 2013;36(2):133–151. doi:10.1097/CJI.0b013e3182829903
  • Ong EZ, Yee JX, Ooi J, et al. Immune gene expression analysis indicates the potential of a self-amplifying Covid-19 mRNA vaccine. NPJ Vaccines. 2022;7(1):154. doi:10.1038/s41541-022-00573-y
  • Francis AG, Elhadd K, Camera V, et al. Acute inflammatory diseases of the central nervous system after SARS-CoV-2 vaccination. Neurol Neuroimmunol Neuroinflamm. 2023;10(1):e200063. doi:10.1212/NXI.0000000000200063
  • Li Y, Fang H, Zhang T, et al. Lipid-mRNA nanoparticles landscape for cancer therapy. Front Bioeng Biotechnol. 2022;10:1053197. doi:10.3389/fbioe.2022.1053197
  • Saha C, Bojdo J, Dunne NJ, Duary RK, Buckley N, McCarthy HO. Nucleic acid vaccination strategies for ovarian cancer. Front Bioeng Biotechnol. 2022;10:953887. doi:10.3389/fbioe.2022.953887
  • Rurik JG, Tombácz I, Yadegari A, et al. CAR T cells produced in vivo to treat cardiac injury. Science. 2022;375(6576):91–96. doi:10.1126/science.abm0594
  • Gao TA, Chen YY. T cells to fix a broken heart. Science. 2022;375(6576):23–24. doi:10.1126/science.abn0851
  • Meister H, Look T, Roth P, et al. Multifunctional mRNA-based CAR T cells display promising antitumor activity against glioblastoma. Clin Cancer Res. 2022;28(21):4747–4756. doi:10.1158/1078-0432.CCR-21-4384
  • Foster JB, Griffin C, Rokita JL, et al. Development of GPC2-directed chimeric antigen receptors using mRNA for pediatric brain tumors. J Immunother Cancer. 2022;10(9):e004450. doi:10.1136/jitc-2021-004450
  • Cherkassky L, Hou Z, Amador-Molina A, Adusumilli PS. Regional CAR T cell therapy: an ignition key for systemic immunity in solid tumors. Cancer Cell. 2022;40(6):569–574. doi:10.1016/j.ccell.2022.04.006
  • Vitanza NA, Ronsley R, Choe M, et al. Locoregional CAR T cells for children with CNS tumors: clinical procedure and catheter safety. Neoplasia. 2023;36:100870. doi:10.1016/j.neo.2022.100870
  • Kovacs ZI, Kim S, Jikaria N, et al. Disrupting the blood-brain barrier by focused ultrasound induces sterile inflammation. Proc Natl Acad Sci U S A. 2017;114(1):E75–E84. doi:10.1073/pnas.1614777114
  • Touat M, Li YY, Boynton AN, et al. Mechanisms and therapeutic implications of hypermutation in gliomas. Nature. 2020;580(7804):517–523. doi:10.1038/s41586-020-2209-9
  • Sanchez-Perez LA, Choi BD, Archer GE, et al. Myeloablative temozolomide enhances CD8⁺ T-cell responses to vaccine and is required for efficacy against brain tumors in mice. PLoS One. 2013;8(3):e59082. doi:10.1371/journal.pone.0059082
  • Restifo NP, Dudley ME, Rosenberg SA. Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol. 2012;12(4):269–281. doi:10.1038/nri3191
  • Porter DL, Hwang WT, Frey NV, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015;7(303):303ra139. doi:10.1126/scitranslmed.aac5415
  • Gardner RA, Finney O, Annesley C, 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):3322–3331. doi:10.1182/blood-2017-02-769208
  • Davies DM, Maher J. Crosstown traffic: lymphodepleting chemotherapy drives CAR T cells. Cancer Cell. 2021;39(2):138–140. doi:10.1016/j.ccell.2020.12.019
  • Straathof K, Flutter B, Wallace R, et al. Antitumor activity without on-target off-tumor toxicity of GD2-chimeric antigen receptor T cells in patients with neuroblastoma. Sci Transl Med. 2020;12(571). doi:10.1126/scitranslmed.abd6169
  • Hong LK, Chen Y, Smith CC, et al. CD30-redirected chimeric antigen receptor T cells target CD30(+) and CD30(-) embryonal carcinoma via antigen-dependent and fas/fasl interactions. Cancer Immunol Res. 2018;6(10):1274–1287. doi:10.1158/2326-6066.CIR-18-0065
  • DeSelm C, Palomba ML, Yahalom J, et al. Low-dose radiation conditioning enables CAR T cells to mitigate antigen escape. Mol Ther. 2018;26(11):2542–2552. doi:10.1016/j.ymthe.2018.09.008
  • Thomas P, Galopin N, Bonérandi E, Clémenceau B, Fougeray S, Birklé S. CAR T cell therapy’s potential for pediatric brain tumors. Cancers. 2021;13(21):5445. doi:10.3390/cancers13215445
  • Murty S, Haile ST, Beinat C, et al. Intravital imaging reveals synergistic effect of CAR T-cells and radiation therapy in a preclinical immunocompetent glioblastoma model. Oncoimmunology. 2020;9(1):1757360. doi:10.1080/2162402X.2020.1757360
  • Weiss T, Weller M, Guckenberger M, Sentman CL, Roth P. NKG2D-based CAR T cells and radiotherapy exert synergistic efficacy in glioblastoma. Cancer Res. 2018;78(4):1031–1043. doi:10.1158/0008-5472.CAN-17-1788
  • Sampson JH, Choi BD, Sanchez-Perez L, et al. EGFRvIII mCAR-modified T-cell therapy cures mice with established intracerebral glioma and generates host immunity against tumor-antigen loss. Clin Cancer Res. 2014;20(4):972–984. doi:10.1158/1078-0432.CCR-13-0709
  • Huan T, Li H, Tang B. Radiotherapy plus CAR-T cell therapy to date: a note for cautions optimism. Front Immunol. 2022;13:1033512. doi:10.3389/fimmu.2022.1033512
  • Jarosz-Biej M, Smolarczyk R, Cichoń T, Kułach N. Tumor microenvironment as A “Game Changer” in cancer radiotherapy. Int J Mol Sci. 2019;20(13):3212. doi:10.3390/ijms20133212
  • Siegel R, Burock S, Wernecke KD, et al. Preoperative short-course radiotherapy versus combined radiochemotherapy in locally advanced rectal cancer: a multi-centre prospectively randomised study of the Berlin Cancer Society. BMC Cancer. 2009;9:50. doi:10.1186/1471-2407-9-50
  • Lanitis E, Rota G, Kosti P, et al. Optimized gene engineering of murine CAR-T cells reveals the beneficial effects of IL-15 coexpression. J Exp Med. 2021;218(2). doi:10.1084/jem.20192203
  • Al-Haideri M, Tondok SB, Safa SH, et al. CAR-T cell combination therapy: the next revolution in cancer treatment. Cancer Cell Int. 2022;22(1):365. doi:10.1186/s12935-022-02778-6
  • Hoyos V, Savoldo B, Quintarelli C, et al. Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia. 2010;24(6):1160–1170. doi:10.1038/leu.2010.75
  • Alizadeh D, Wong RA, Yang X, et al. IL15 enhances CAR-T cell antitumor activity by reducing mTORC1 activity and preserving their stem cell memory phenotype. Cancer Immunol Res. 2019;7(5):759–772. doi:10.1158/2326-6066.CIR-18-0466
  • Tang L, Zheng Y, Melo MB, et al. Enhancing T cell therapy through TCR-signaling-responsive nanoparticle drug delivery. Nat Biotechnol. 2018;36(8):707–716. doi:10.1038/nbt.4181
  • Brown CE, Rodriguez A, Palmer J, et al. Off-The-shelf, steroid-resistant, IL13Rα2-specific CAR T cells for treatment of glioblastoma. Neuro Oncol. 2022;24(8):1318–1330. doi:10.1093/neuonc/noac024
  • Yoon DH, Osborn MJ, Tolar J, Kim CJ. Incorporation of immune checkpoint blockade into Chimeric Antigen Receptor T Cells (CAR-Ts): combination or built-in CAR-T. Int J Mol Sci. 2018;19(2). doi:10.3390/ijms19020340
  • Tang OY, Tian L, Yoder T, et al. PD1 expression in EGFRvIII-directed CAR T cell infusion product for glioblastoma is associated with clinical response. Front Immunol. 2022;13:872756. doi:10.3389/fimmu.2022.872756
  • DiDomenico J, Lamano JB, Oyon D, et al. The immune checkpoint protein PD-L1 induces and maintains regulatory T cells in glioblastoma. Oncoimmunology. 2018;7(7):e1448329. doi:10.1080/2162402X.2018.1448329
  • Gargett T, Yu W, Dotti G, et al. GD2-specific CAR T cells undergo potent activation and deletion following antigen encounter but can be protected from activation-induced cell death by PD-1 blockade. Mol Ther. 2016;24(6):1135–1149. doi:10.1038/mt.2016.63
  • Davidson TB, Lee A, Hsu M, et al. Expression of PD-1 by T cells in malignant glioma patients reflects exhaustion and activation. Clin Cancer Res. 2019;25(6):1913–1922. doi:10.1158/1078-0432.CCR-18-1176
  • Kuramitsu S, Ohno M, Ohka F, et al. Lenalidomide enhances the function of chimeric antigen receptor T cells against the epidermal growth factor receptor variant III by enhancing immune synapses. Cancer Gene Ther. 2015;22(10):487–495. doi:10.1038/cgt.2015.47
  • Wang Z, Zhou G, Risu N, et al. Lenalidomide enhances CAR-T cell activity against solid tumor cells. Cell Transplant. 2020;29:963689720920825. doi:10.1177/0963689720920825
  • Demaria O, Cornen S, Daëron M, Morel Y, Medzhitov R, Vivier E. Harnessing innate immunity in cancer therapy. Nature. 2019;574(7776):45–56. doi:10.1038/s41586-019-1593-5
  • Ma L, Dichwalkar T, Chang J, et al. Enhanced CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptor. Science. 2019;365(6449):162–168. doi:10.1126/science.aav8692
  • Sun T, Li Y, Yang Y, Liu B, Cao Y, Yang W. Enhanced radiation-induced immunogenic cell death activates chimeric antigen receptor T cells by targeting CD39 against glioblastoma. Cell Death Dis. 2022;13(10):875. doi:10.1038/s41419-022-05319-1
  • Altinoz MA, Ozpinar A, Hacker E, Ozpinar A. Combining locoregional CAR-T cells, autologous + allogeneic tumor lysate vaccination and levamisole in treatment of glioblastoma. Immunopharmacol Immunotoxicol. 2022;44(6):797–808. doi:10.1080/08923973.2022.2086136
  • Huang M, Deng J, Gao L, Zhou J. Innovative strategies to advance CAR T cell therapy for solid tumors. Am J Cancer Res. 2020;10(7):1979–1992.
  • Watanabe K, Luo Y, Da T, et al. Pancreatic cancer therapy with combined mesothelin-redirected chimeric antigen receptor T cells and cytokine-armed oncolytic adenoviruses. JCI Insight. 2018;3(7). doi:10.1172/jci.insight.99573
  • Tanoue K, Rosewell Shaw A, Watanabe N, et al. Armed oncolytic adenovirus-expressing PD-L1 mini-body enhances antitumor effects of chimeric antigen receptor T cells in solid tumors. Cancer Res. 2017;77(8):2040–2051. doi:10.1158/0008-5472.CAN-16-1577
  • Wing A, Fajardo CA, Posey AD Jr, et al. Improving CART-cell therapy of solid tumors with oncolytic virus-driven production of a bispecific T-cell engager. Cancer Immunol Res. 2018;6(5):605–616. doi:10.1158/2326-6066.CIR-17-0314
  • Huang J, Zheng M, Zhang Z, et al. Interleukin-7-loaded oncolytic adenovirus improves CAR-T cell therapy for glioblastoma. Cancer Immunol Immunother. 2021;70(9):2453–2465. doi:10.1007/s00262-021-02856-0
  • Evgin L, Kottke T, Tonne J, et al. Oncolytic virus-mediated expansion of dual-specific CAR T cells improves efficacy against solid tumors in mice. Sci Transl Med. 2022;14(640):eabn2231. doi:10.1126/scitranslmed.abn2231
  • Liu Z, Zhou J, Yang X, et al. Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma. Mol Cancer. 2023;22(1):3. doi:10.1186/s12943-022-01711-9
  • Zhang G, Zhao Y, Liu Z, et al. GD2 CAR-T cells in combination with Nivolumab exhibit enhanced antitumor efficacy. Transl Oncol. 2023;32:101663. doi:10.1016/j.tranon.2023.101663
  • Nakagawa T, Kijima N, Hasegawa K, et al. Identification of glioblastoma-specific antigens expressed in patient-derived tumor cells as candidate targets for chimeric antigen receptor T cell therapy. Neurooncol Adv. 2023;5(1):vdac177. doi:10.1093/noajnl/vdac177