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Car-Engineered Nk Cells Versus Car T Cells in Treatment of Glioblastoma; Strength and Flaws Publisher Pubmed



Sabahi M1 ; Fathi Jouzdani A2, 3 ; Sadeghian Z4 ; Dabbagh Ohadi MA5 ; Sultan H6 ; Salehipour A2, 3 ; Maniakhina L7 ; Rezaei N8, 9 ; Adada B1 ; Mansouri A10 ; Borgheirazavi H1
Authors
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Authors Affiliations
  1. 1. Department of Neurological Surgery, Pauline Braathen Neurological Center, Cleveland Clinic Florida, Weston, FL, United States
  2. 2. Neurosurgery Research Group (NRG), Hamadan University of Medical Sciences, Hamadan, Iran
  3. 3. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pathology & Laboratory Medicine, Cleveland Clinic Florida, Weston, FL, United States
  5. 5. Department of Neurosurgery, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, United States
  7. 7. Department of Neurosurgery, Geisinger and Geisinger Commonwealth School of Medicine, Wilkes-Barre, PA, United States
  8. 8. Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
  9. 9. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  10. 10. Department of Neurosurgery, Penn State Milton S. Hershey Medical Center, Hershey, PA, United States

Source: Journal of Neuro-Oncology Published:2025


Abstract

Glioblastoma (GBM) is a highly aggressive primary brain tumor that carries a grim prognosis. Because of the dearth of treatment options available for treatment of GBM, Chimeric Antigen Receptor (CAR)-engineered T cell and Natural Killer (NK) therapy could provide alternative strategies to address the challenges in GBM treatment. In these approaches, CAR T and NK cells are engineered for cancer-specific immunotherapy by recognizing surface antigens independently of major histocompatibility complex (MHC) molecules. However, the efficacy of CAR T cells is hindered by GBM’s downregulation of its targeted antigens. CAR NK cells face similar challenges, but, in contrast, they offer advantages as off-the-shelf allogeneic products, devoid of graft-versus-host disease (GVHD) risk as well as anti-cancer activity beyond CAR specificity, potentially reducing the risk of relapse or resistance. Despite CAR T cell therapies being extensively studied in clinical settings, the use of CAR-modified NK cells in GBM treatment remains largely in the preclinical stage. This review aims to discuss recent advancements in NK cell and CAR T cell therapies for GBM, including methods for introducing CARs into both NK cells and T cells, addressing manufacturing challenges, and providing evidence supporting the efficacy of these approaches from preclinical and early-phase clinical studies. The comprehensive evaluation of CAR-engineered NK cells and CAR T cells seeks to identify the optimal therapeutic approach for GBM, contributing to the development of effective immunotherapies for this devastating disease. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.
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