Engineered Cells As Glioblastoma Therapeutics

Overview

Journal Cancer Gene Ther

Specialties Genetics
Oncology
Pharmacology

Date 2021 Mar 23

PMID 33753869

Citations 7

Authors

Aparna Ramanathan

Ian A J Lorimer

Affiliations

Soon will be listed here.

Abstract

In spite of significant recent advances in our understanding of the genetics and cell biology of glioblastoma, to date, this has not led to improved treatments for this cancer. In addition to small molecule, antibody, and engineered virus approaches, engineered cells are also being explored as glioblastoma therapeutics. This includes CAR-T cells, CAR-NK cells, as well as engineered neural stem cells and mesenchymal stem cells. Here we review the state of this field, starting with clinical trial studies. These have established the feasibility and safety of engineered cell therapies for glioblastoma and show some evidence for activity. Next, we review the preclinical literature and compare the strengths and weaknesses of various starting cell types for engineered cell therapies. Finally, we discuss future directions for this nascent but promising modality for glioblastoma therapy.

Citing Articles

Fructose 1,6-bisphosphatase 1 is a potential biomarker affecting the malignant phenotype and aerobic glycolysis in glioblastoma.

Lu W, Huang G, Yu Y, Zhai X, Zhou X PeerJ. 2025; 13:e18926.

PMID: 39902328 PMC: 11789649. DOI: 10.7717/peerj.18926.

Extracellular adenosine oppositely regulates the purinome machinery in glioblastoma and mesenchymal stem cells.

Pietrobono D, Russo L, Bertilacchi M, Marchetti L, Martini C, Giacomelli C IUBMB Life. 2024; 76(12):1234-1251.

PMID: 39134088 PMC: 11580377. DOI: 10.1002/iub.2905.

Hallmarks of the Tumour Microenvironment of Gliomas and Its Interaction with Emerging Immunotherapy Modalities.

Linares C, Varghese A, Ghose A, Shinde S, Adeleke S, Sanchez E Int J Mol Sci. 2023; 24(17).

PMID: 37686020 PMC: 10487469. DOI: 10.3390/ijms241713215.

Anti-Cancer Effect of Neural Stem Cells Transfected with Carboxylesterase and sTRAIL Genes in Animals with Brain Lesions of Lung Cancer.

Kim J, Ahn J, Lee D, Hong S, Lee H Pharmaceuticals (Basel). 2023; 16(8).

PMID: 37631070 PMC: 10458428. DOI: 10.3390/ph16081156.

Extracellular LGALS3BP: a potential disease marker and actionable target for antibody-drug conjugate therapy in glioblastoma.

Dufrusine B, Capone E, Ponziani S, Lattanzio R, Lanuti P, Giansanti F Mol Oncol. 2023; 17(8):1460-1473.

PMID: 37195369 PMC: 10399712. DOI: 10.1002/1878-0261.13453.

References

Brennan C, Verhaak R, McKenna A, Campos B, Noushmehr H, Salama S . The somatic genomic landscape of glioblastoma. Cell. 2013; 155(2):462-77. PMC: 3910500. DOI: 10.1016/j.cell.2013.09.034. View

Verhaak R, Hoadley K, Purdom E, Wang V, Qi Y, Wilkerson M . 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. PMC: 2818769. DOI: 10.1016/j.ccr.2009.12.020. View

Patel A, Tirosh I, Trombetta J, Shalek A, Gillespie S, Wakimoto H . Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Science. 2014; 344(6190):1396-401. PMC: 4123637. DOI: 10.1126/science.1254257. View

Barthel F, Johnson K, Varn F, Moskalik A, Tanner G, Kocakavuk E . Longitudinal molecular trajectories of diffuse glioma in adults. Nature. 2019; 576(7785):112-120. PMC: 6897368. DOI: 10.1038/s41586-019-1775-1. View

Lan X, Jorg D, Cavalli F, Richards L, Nguyen L, Vanner R . Fate mapping of human glioblastoma reveals an invariant stem cell hierarchy. Nature. 2017; 549(7671):227-232. PMC: 5608080. DOI: 10.1038/nature23666. View

Neftel C, Laffy J, Filbin M, Hara T, Shore M, Rahme G . An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma. Cell. 2019; 178(4):835-849.e21. PMC: 6703186. DOI: 10.1016/j.cell.2019.06.024. View

Osswald M, Jung E, Sahm F, Solecki G, Venkataramani V, Blaes J . Brain tumour cells interconnect to a functional and resistant network. Nature. 2015; 528(7580):93-8. DOI: 10.1038/nature16071. View

Osswald M, Solecki G, Wick W, Winkler F . A malignant cellular network in gliomas: potential clinical implications. Neuro Oncol. 2016; 18(4):479-85. PMC: 4799690. DOI: 10.1093/neuonc/now014. View

Weil S, Osswald M, Solecki G, Grosch J, Jung E, Lemke D . Tumor microtubes convey resistance to surgical lesions and chemotherapy in gliomas. Neuro Oncol. 2017; 19(10):1316-1326. PMC: 5596180. DOI: 10.1093/neuonc/nox070. View

10.

Stupp R, Mason W, van den Bent M, Weller M, Fisher B, Taphoorn M . Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005; 352(10):987-96. DOI: 10.1056/NEJMoa043330. View

11.

Brown P, Krishnan S, Sarkaria J, Wu W, Jaeckle K, Uhm J . Phase I/II trial of erlotinib and temozolomide with radiation therapy in the treatment of newly diagnosed glioblastoma multiforme: North Central Cancer Treatment Group Study N0177. J Clin Oncol. 2008; 26(34):5603-9. PMC: 2651097. DOI: 10.1200/JCO.2008.18.0612. View

12.

van den Bent M, Brandes A, Rampling R, Kouwenhoven M, Kros J, Carpentier A . Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. J Clin Oncol. 2009; 27(8):1268-74. PMC: 2667826. DOI: 10.1200/JCO.2008.17.5984. View

13.

Cloughesy T, Mochizuki A, Orpilla J, Hugo W, Lee A, Davidson T . Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. Nat Med. 2019; 25(3):477-486. PMC: 6408961. DOI: 10.1038/s41591-018-0337-7. View

14.

Guedan S, Ruella M, June C . Emerging Cellular Therapies for Cancer. Annu Rev Immunol. 2018; 37:145-171. PMC: 7399614. DOI: 10.1146/annurev-immunol-042718-041407. View

15.

Yip A, Webster R . The market for chimeric antigen receptor T cell therapies. Nat Rev Drug Discov. 2018; 17(3):161-162. DOI: 10.1038/nrd.2017.266. View

16.

Brown C, Badie B, Barish M, Weng L, Ostberg J, Chang W . Bioactivity and Safety of IL13Rα2-Redirected Chimeric Antigen Receptor CD8+ T Cells in Patients with Recurrent Glioblastoma. Clin Cancer Res. 2015; 21(18):4062-72. PMC: 4632968. DOI: 10.1158/1078-0432.CCR-15-0428. View

17.

Kahlon K, Brown C, Cooper L, Raubitschek A, Forman S, Jensen M . Specific recognition and killing of glioblastoma multiforme by interleukin 13-zetakine redirected cytolytic T cells. Cancer Res. 2004; 64(24):9160-6. DOI: 10.1158/0008-5472.CAN-04-0454. View

18.

Brown C, Alizadeh D, Starr R, Weng L, Wagner J, Naranjo A . Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy. N Engl J Med. 2016; 375(26):2561-9. PMC: 5390684. DOI: 10.1056/NEJMoa1610497. View

19.

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

20.

Pule M, Savoldo B, Myers G, Rossig C, Russell H, Dotti G . Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nat Med. 2008; 14(11):1264-70. PMC: 2749734. DOI: 10.1038/nm.1882. View