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Treatment of glioblastoma with genetic engineering
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Touraj Naderi   , Mahsa Zamani , Negar Zamani Alavijeh , Mehregan Noghreh |
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Abstract: (235 Views) |
Introduction: Gliomas account for almost 30% of primary brain tumors Based on their histopathological features, gliomas are traditionally classified by the World Health Organization (WHO) as grade I and II (low-grade gliomas), grade III (anaplastic) and IV (glioblastoma), which indicate different degrees of malignancy. Tumor immunogenicity is induced by the antitumor activities of dendritic cells (DCs) and macrophages which activate the tumor-associated antigens (TAAs)-specific T cells resulting in the production of necessary cytokines and engagement of T cells, natural killer (NK) cells, and B cells, all providing antitumor cytotoxicity. The genetic and cellular heterogeneity of the surrounding tumor microenvironment (TME) complicated the clinical efficacy of those treatments. Along with the genetic and epigenetic instabilities, the nongenetic intra-tumor heterogeneity and plasticity conduct therapy failure due to the presence of the rare population of cancerous cells known as cancer stem cells (CSCs) or cancer-initiating cells (CICs).
Search Method: Keywords were searched in the Google and PubMed databases to find documents related to writing a review article.
Results: The presence of exhausted T cells in the tumor microenvironment indicates that inhibitory receptors are overexpressed, reducing the production of effector cytokines and cytolytic activity, leading to failure in cancer elimination. Exhausted T cells express high levels of inhibitory receptors, including programmed cell death protein 1 (PD-1), lymphocyte activation gene 3 protein (LAG-3), T-cell immunoglobulin domain and mucin domain protein 3 (TIM-3), cytotoxic T lymphocyte antigen-4 (CTLA-4), band T lymphocyte attenuator (BTLA) and T-cell immunoglobulin.
Conclusions: Chimeric antigen receptors (CARs) are engineered fusion proteins constructed from antigen recognition, signaling, and costimulatory domains that can be expressed in cytotoxic T cells with the purpose of reprograming the T cells to specifically target tumor cells. CAR T-cell therapy uses gene transfer technology to reprogram a patient's own T cells to stably express CARs, thereby combining the specificity of an antibody with the potent cytotoxic and memory functions of a T cell.
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| Keywords: T-cell therapy, (CAR), Genetic engineering, Immunotherapy |
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Full-Text [PDF 253 kb]
(32 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2024/01/30 | Accepted: 2023/08/23 | Published: 2023/08/23
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