Potential of Glioblastoma-Targeted Chimeric Antigen Receptor (CAR) T-Cell Therapy
Autor: | Ryan D Salinas, Joseph S. Durgin, Donald M. O'Rourke |
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Rok vydání: | 2020 |
Předmět: |
T-Lymphocytes
medicine.medical_treatment Receptors Antigen T-Cell Brain tumor Immunotherapy Adoptive 03 medical and health sciences 0302 clinical medicine Pharmacotherapy Antigen medicine Animals Humans Pharmacology (medical) Receptors Chimeric Antigen Brain Neoplasms business.industry Immunosuppression Immunotherapy medicine.disease Chimeric antigen receptor 030227 psychiatry Clinical trial Psychiatry and Mental health Cancer research Neurology (clinical) Glioblastoma business 030217 neurology & neurosurgery |
Zdroj: | CNS Drugs. 34:127-145 |
ISSN: | 1179-1934 1172-7047 |
Popis: | Despite the established efficacy of chimeric antigen receptor (CAR) T-cell therapy in hematologic malignancies, translating CAR T therapy to solid tumors has remained investigational. Glioblastoma, the most aggressive and lethal form of primary brain tumor, has recently been among the malignancies being trialed clinically with CAR T cells. Glioblastoma in particular holds several unique features that have hindered clinical translation, including its vast intertumoral and intratumoral heterogeneity, associated immunosuppressive environment, and lack of clear experimental models to predict response and analyze resistant phenotypes. Here, we review the history of CAR T therapy development, its current progress in treating glioblastoma, as well as the current challenges and future directions in establishing CAR T therapy as a viable alternative to the current standard of care. Tremendous efforts are currently ongoing to identify novel CAR targets and target combinations for glioblastoma, to modify T cells to enhance their efficacy and to enable them to resist tumor-mediated immunosuppression, and to utilize adjunct therapies such as lymphodepletion, checkpoint inhibition, and bi-specific engagers to improve CAR T persistence. Furthermore, new preclinical models of CAR T therapy are being developed that better reflect the clinical features seen in human trials. Current clinical trials that rapidly incorporate key preclinical findings to patient translation are emerging. |
Databáze: | OpenAIRE |
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