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Salehi Nezamabadi, Sasan, Safari Sabet, Arash, Sadat Peighambardoust, Sana, Behrouzieh, Sadra, Banihashemi, Seyed Reza, Amanpour, Saeid. (1404). Exploring CD19-targeted Immunotherapy Strategies for human B-cell lymphoma. سامانه مدیریت نشریات علمی, 80(2), 301-312. doi: 10.32592/ARI.2025.80.2.301
Sasan Salehi Nezamabadi; Arash Safari Sabet; Sana Sadat Peighambardoust; Sadra Behrouzieh; Seyed Reza Banihashemi; Saeid Amanpour. "Exploring CD19-targeted Immunotherapy Strategies for human B-cell lymphoma". سامانه مدیریت نشریات علمی, 80, 2, 1404, 301-312. doi: 10.32592/ARI.2025.80.2.301
Salehi Nezamabadi, Sasan, Safari Sabet, Arash, Sadat Peighambardoust, Sana, Behrouzieh, Sadra, Banihashemi, Seyed Reza, Amanpour, Saeid. (1404). 'Exploring CD19-targeted Immunotherapy Strategies for human B-cell lymphoma', سامانه مدیریت نشریات علمی, 80(2), pp. 301-312. doi: 10.32592/ARI.2025.80.2.301
Salehi Nezamabadi, Sasan, Safari Sabet, Arash, Sadat Peighambardoust, Sana, Behrouzieh, Sadra, Banihashemi, Seyed Reza, Amanpour, Saeid. Exploring CD19-targeted Immunotherapy Strategies for human B-cell lymphoma. سامانه مدیریت نشریات علمی, 1404; 80(2): 301-312. doi: 10.32592/ARI.2025.80.2.301

Exploring CD19-targeted Immunotherapy Strategies for human B-cell lymphoma

Archives of Razi Institute
مقاله 5، دوره 80، شماره 2، خرداد و تیر 2025، صفحه 301-312    اصل مقاله (455.34 K)
نوع مقاله: Review Article
شناسه دیجیتال (DOI): 10.32592/ARI.2025.80.2.301
نویسندگان
Sasan Salehi Nezamabadi1؛ Arash Safari Sabet1؛ Sana Sadat Peighambardoust1؛ Sadra Behrouzieh1؛ Seyed Reza Banihashemi2؛ Saeid Amanpour* 3
1School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
2Department of Immunology, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj P.O. Box 31975/148, Iran
3Cancer biology research center, Tehran University of medical sciences, Tehran, Iran
چکیده
B-cell lymphomas (BCLs) comprise approximately 40 subtypes resulting from mature B-cells' malignant transformation. BCLs are treated differently based on the type and stage of the lymphoma. Multiple therapeutic options exist, including chemotherapy, immunotherapy, radiation therapy, targeted therapy, and stem cell transplantation. Among them, targeted therapy has shown great potential for safer and more effective treatment. Targeted therapies include monoclonal antibodies and nanobodies, CAR-T cell therapies, and Bispecific T-cell engager (BiTE), which operate in diverse ways by targeting a number of molecules including CD79b, CD20, CD30, CD52, and CD19. CD19 is an immunoglobulin superfamily transmembrane glycoprotein of type I which is necessary for setting intrinsic B-cell signaling thresholds by tempering both receptor-dependent and receptor-independent signaling. According to the limitations of conventional therapies and other targets, it seems that CD19 is a proper target for lymphoma. There are several FDA-approved anti-CD19 CAR-T cells such as Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel, and Anti-CD19 Monoclonal Antibodies (mABs) such as Loncastuximab Tesirine and Tafasitamab, for which more than a few clinical trials have shown trustworthy results. Blinatumomab is the first FDA-approved antibody produced using BiTE technology which has shown good benefits in B-cell ALL treatment clinical trials. Single-domain antibodies (sdAb) or nanobodies, are the nanoscale VHH fragments of heavy chain-only antibodies (HcAbs) and have been utilized in conjunction with CAR T-cells, yielding promising outcomes. In this review, we aimed to discuss CD19 as an auspicious therapeutic target for lymphoma. Moreover, we talked about different treatment options regarding CD19 targeting, along with the relevant clinical studies, for each of which, the efficacy, safety, and limitations were elaborated.
کلیدواژه‌ها
CD-19 Antigen؛ Molecular Targeted Therapy؛ Lymphoma؛ CAR-T cell؛ Monoclonal Antibody
عنوان مقاله [English]
بررسی استراتژی های ایمونوتراپی با هدف CD19 برای درمان لنفوم سلول B انسانی
چکیده [English]
لنفوم های سلول B (BCLs) تقریباً 40 زیرگروه را تشکیل می دهند که از تغییرشکل بدخیم سلول های B بالغ به وجود می آیند. بدخیمی های سلول های B بر اساس نوع و مرحله لنفوم به طور متفاوتی درمان می شوند. گزینه های درمانی متعددی از جمله شیمی درمانی، ایمونوتراپی، پرتودرمانی، درمان های هدفمند و پیوند سلول های بنیادی برای این مشکل وجود دارند. درمیان آنها، درمان های هدفمند ظرفیت زیادی برای درمان ایمن تر و موثرتر نشان داده اند. درمان‌های هدفمند شامل آنتی‌بادی‌ها و نانوبادی‌های مونوکلونال، درمان‌ با سلول‌های CAR-T و گیرنده سلول‌های T Bispecific (BiTE) هستند که به روش‌های مختلف با هدف قرار دادن چندین مولکول از جمله CD79b، CD20، CD30، CD52 و CD19 عمل می‌کنند. CD19 یک گلیکوپروتئین ترانس ممبران از خانواده ایمونوگلوبولین های نوع یک است که برای تنظیم آستانه سیگنال دهی ذاتی سلول B با تعدیل سیگنال دهی وابسته به گیرنده و مستقل از گیرنده ضروری است. با توجه به محدودیت های درمان های مرسوم و سایر موارد به نظر می رسد CD19 هدف مناسبی برای درمان لنفوم باشد. چندین سلولCAR-T مورد تایید FDA علیهCD19 مانند Axicabtagene Ciloleucel، Tisagenlecleucel، و Lisocabtagene Maraleucel، و آنتی بادی های مونوکلونال Anti-CD19 (mABs) مانند Loncastuximab Tesirine و Tafasitamab وجود دارند که بیش از چند مورد آزمایش بالینی برای آنها انجام گرفته است. نتایج قابل اعتماد Blinatumomab اولین آنتی بادی تایید شده توسط FDA که با استفاده از فناوری BiTE تولید شده است مزایای خوبی در آزمایشات بالینی درمان ALL سلول B نشان داده است. آنتی‌بادی‌های تک دامنه (sdAb) یا نانوبادی‌ها، قطعات VHH در مقیاس نانو از آنتی‌بادی‌های زنجیره سنگین (HcAbs) هستند که در ارتباط با سلول‌های T CAR مورد استفاده قرار گرفته‌اند و نتایج امیدوارکننده‌ای را به همراه دارند. در این بررسی، هدف ما بررسی CD19 به عنوان یک هدف درمانی مناسب برای لنفوم بود. علاوه بر این، گزینه های درمانی مختلف برای هدف قرار دادن مولکول CD19، همراه با مطالعات بالینی مربوطه مورد بحث قرار گرفتند که برای هر یک از آنها، اثربخشی، ایمنی و محدودیت ها توضیح داده شدند.
کلیدواژه‌ها [English]
آنتی ژن CD-19, درمان هدفمند مولکولی, لمفوم, سلول CAR-T, آنتی بادی مونوکلونال
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