Effectiveness of CAR T-cell Therapy in Improving Overall Survival in Patients with Glioblastoma Multiforme Compared to Conventional Chemotherapy: A Systematic Review
Yahir Chico-Alcaraz1, María Aguilar López2, David Jeshua Resendiz Daniel3, José Miguel Perales Vaquera4, Thania Estrada Ortega1, Emma de la Salud Pahua Mota5, Karla Guevara1, Marcos Arreola Flores1, Miguel Solis Lecuona1, Luis Hernandez Rangel6, Oziel Gonzalez Godoy1, Angel Martinez Hernandez1, Sara Gomez7
1Universidad Autónoma de San Luis Potosí, 2Universidad Veracruzana Región Córdoba-Orizaba, 3Universidad Autónoma del Estado de Hidalgo, 4Universidad Cuauhtémoc Plantel Aguascalientes, 5Universidad Michoacana de San Nicolás de Hidalgo - Facultad de Ciencias Médicas y Biológicas Dr Ignacio Chávez, 6Universidad Veracruzana Región Poza Rica - Tuxpan, 7Universidad Autonoma de Durango Campus Torreón
Objective:
Determine if CAR T-cell therapy significantly improves overall survival compared to conventional chemotherapy in patients diagnosed with glioblastoma multiforme.
Background:
Glioblastoma multiforme, the most common and one of the deadliest primary brain tumors, has a bleak prognosis with conventional treatments. However, recurrence is universal, leading to low overall survival. The emergence of CAR T-cell therapy offers a ray of hope. CAR T-cell therapy aims to induce cytotoxicity against malignant cells to eliminate them. Preliminary studies indicate potential efficacy, but further evaluation against existing treatments is necessary.
Design/Methods:
Utilizing articles from the AAN database, PubMed, and Cochrane. Initially, relevant articles were summarized. We analyzed experimental studies, specifically the ones that include CAR T-cell therapy among predominantly review articles on all kinds of treatment. Findings were synthesized by examining key points from both review and experimental literature, highlighting specific CAR T-cell therapy treatments under investigation against GBM and its comparison to conventional treatment.
Results:
CAR T-cell therapy clinical trials with antigens like EGFRvIII, NKG2D, B7-H3, CD147, IL13Ralpha2, HER2, and GD2 demonstrate significant, albeit limited, improvements over conventional treatments for glioblastoma multiforme (recurrent and non-recurrent), extending survival by approximately 1 to 9 months on phase I trials. However, its efficacy is restricted to patients with specific overexpressed antigens. Additionally, tumor microenvironment-induced immune suppression and tumor cell resistance pose substantial challenges to treatment effectiveness. Better results have been achieved with double-targeted treatments using nanoparticles, which have shown superior efficacy and better distribution in the tumor.
Conclusions:
CAR T-cell therapy demonstrates limited but promising improvements over conventional treatments in overall survival in phase I studies. Although their effectiveness is almost restricted to patients with specific overexpressed antigens and recurrent GBM, and challenges such as tumor-induced immune suppression and resistance remain. While this review's findings bring hope, they also underscore the urgent need for further and more hope research.
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