Chimeric antigen receptor -T cell therapy: Applications and challenges in treatment of allergy and asthma

被引:46
作者
Esmaeilzadeh, Abdolreza [1 ,2 ]
Tahmasebi, Safa [3 ]
Athari, Seyyed Shamsadin [1 ]
机构
[1] Zanjan Univ Med Sci, Sch Med, Dept Immunol, Zanjan, Iran
[2] Zanjan Univ Med Sci, Canc Gene Therapy Res Ctr CGRC, Zanjan, Iran
[3] Univ Tehran Med Sci, Hlth Fac, Dept Immunol, Tehran, Iran
关键词
Adoptive cell therapy; CAR-T cell; Allergy; Asthma; T regulatory cells; Immunotherapy; ACUTE LYMPHOBLASTIC-LEUKEMIA; REGULATORY CELLS; ANTITUMOR-ACTIVITY; AIRWAY INFLAMMATION; SELECTIVE EXPANSION; CYTOPLASMIC DOMAIN; PERIPHERAL-BLOOD; B-CELL; CAR; TUMOR;
D O I
10.1016/j.biopha.2019.109685
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Despite the current advancements, cancer treatment approaches have limitations restricting their cure rate. Immunotherapy techniques are among novel and promising cancer therapeutic approaches. Therapeutic antibodies and adoptive cell therapy (ACT) are the main branches of immunotherapy. T lymphocytes and genetically engineered cells are among important cells which can be used in ACT. This review has focused on recent advances in engineered cell-based immunotherapy based on T lymphocytes with chimeric antigen receptors (CARs). CARs are recombinant receptors expressing T cell signaling domains with or without co-stimulatory molecules. CAR-T cells are expanded ex vivo and re-infused to patients in order to improve their therapeutic efficacy. Nowadays, the beneficial function of CAR-T cell therapy has been indicated in various diseases including hematological malignancies, solid tumors, autoimmune diseases, and allergic diseases such as asthma. Furthermore, antigen-specific T regulatory cells (T-regs) and gene-edited T cells seem to be beneficial in controlling inflammation in allergic asthma. In fact, dysregulated function of T-regs is responsible for dominance of T helper 2 immune response and progression of allergic asthma. CAR-T-reg cells can also be designed and reproduced using iT(reg) population to manage asthma. In addition, universal CAR-T cells can be modified to selectively target multiple antigens. The fourth generation CAR-T cells (i.e. TRUCK cells) represent novel strategies to cure asthma and allergic diseases as well. Despite the advantages of CAR-T cells, their applications can be associated with some unwanted reactions such as cytokine storm, anaphylaxis, neurotoxicity, etc. For clinical application, there is a need to prevent and manage these complications by optimizing ACT protocols.
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页数:13
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