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صفحه اصلی
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اولین کنگره بین المللی رویکردهای نوین سبک زندگی، پیشگیری و درمان سرطان
CAR T-cell Based Gene Therapy For Cancer: new perspectives and challenges systematic review
نویسندگان :
Fatemeh Aboutorabzadeh (دانشگاه آزاد اسلامی واحد مشهد) , Jalal Ghorbani (دانشگاه آزاد اسلامی واحد مشهد) , Fatemeh Abiat (دانشگاه آزاد اسلامی واحد مشهد) , Hedyeh Anbiaie (دانشگاه آزاد اسلامی واحد مشهد)
کلمات کلیدی :
car t-cell،car t-cell therapy،immunotherapy،hematological malignancy
چکیده :
Background: In this review, we briefly discussed cancer immunotherapy, the genetic engineering of T cells In detail, and the current innovations in CAR T-cell strategies in hematologic malignancies. Furthermore, we also discussed the current challenges in CAR T-cell therapy. CAR-T cell therapy is a novel and rapidly evolving cellular immunotherapy that has achieved significant long-term durable remission in cancer patients compared to traditional cancer therapies. Methods: this study was a review study that conducted by using Screening title/abstract and full manuscript in PubMed database. Finally 15 out of 384 results were examined in detail. These studies were published between 2000 and 2023. Results: development and employment of new treatment concepts have been initiated to further improve overall survival and reduce cancer burden, while inducing lower systemic toxicity. One of them was immunotherapy, which uses antibodies, cytokines, and immune cells to modulate the host immune response to cancer. Chimeric antigen receptor T (CAR-T) cell therapy is regarded as an effective solution for relapsed or refractory tumors, particularly for hematological malignancies. These strategies are based on the infusion of lymphocytes, usually autologous T cells, to fight disease in patients. By selecting or modifying the lymphocytes’ specificity towards a target antigen, they are expanded and injected back into the patient, where they exert their cytotoxic activity and help to mount a sustained immune response against it. CAR T cells are T lymphocytes genetically modified with an appropriate DNA construct, which endows them with expression of a CAR, a fusion protein between a ligand-specific recognition domain, often an antibody-like structure, and the activating signaling domain of the T cell receptor. Activated CAR T cells secrete cytokines, such as IL-2, IL-6, and IFN-γ, that recruit and potentiate the action of other immune cells, like NK cells, macrophages, and other T cells, orchestrating a more robust tumor-suppressive environment. CAR-T cells with flaws in CAR design and functional defects may reduce anti-tumor efficacy and durable remission. CAR-transduced T lymphocytes, especially anti CD19-CAR T cells, have displayed impressive efficacy in patients with B cell malignancies, such as chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), particularly relapsed/refractory B-ALL, non-Hodgkin lymphoma (NHL), and multiple myeloma(MM). Despite the relative effectiveness of transduced-CAR T cells in patients with hematological malignancies, it fails to enable marked anti-tumor response in the treatment of solid tumors. Conclusions: CAR-T cells are the best-in-class example of genetic engineering of T cells, bringing us spectacular opportunities and hopefully entering the mainstream of cancer therapy for B cell malignancies in the next 1–2 years. Following CAR-modified T cells striking success in hematological malignancies, they have been proposed as a novel curative strategy in solid tumors. It has encountered challenges such as lymphocyte penetration into the tumor tissue or exhaustion by the immunosuppressive tumor milieu. Many challenges remain, however, as we strive to make remissions induced by this therapy durable for all treated patients. Legal entity responsible for the study: the authors Funding: no funding Disclosure: no conflicts of interest Keywords: CAR T-cell, CAR T-cell therapy, immunotherapy, hematological malignancy
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