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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
مراجع
  1. de Leval L, Jaffe ES. Lymphoma Classification. The Cancer Journal. 2020;26(3):176-85.
  2. Dalla-Favera R, Pasqualucci L. Chapter 22 - Molecular Pathogenesis of B Cell Lymphomas. In: Alt FW, Honjo T, Radbruch A, Reth M, editors. Molecular Biology of B Cells (Second Edition). London: Academic Press. 2015. p. 399-416.
  3. Cancer Tomorrow. International Agency for Research on Cancer (IARC). Available from: https://gco.iarc.fr/tomorrow
  4. American Cancer Society. Non-Hodgkin Lymphoma (Adults). American Cancer Society; c2023. Available from: https://www.cancer.org/cancer/types/non-hodgkin-lymphoma.html.
  5. Coiffier B. Rituximab in the treatment of diffuse large B-cell lymphomas. Seminars in Oncology. 2002;29(2):30-5.
  6. Cerny T, Borisch B, Introna M, Johnson P, Rose AL. Mechanism of action of rituximab. Anti-cancer drugs. 2002;13:S3-10.
  7. Wang K, Wei G, Liu D. CD19: a biomarker for B cell development, lymphoma diagnosis and therapy. Experimental hematology & oncology. 2012;1(1):1-7.
  8. Lin H, Cheng J, Mu W, Zhou J, Zhu L. Advances in Universal CAR-T Cell Therapy. Frontiers in Immunology. 2021;12.
  9. Labanieh L, Majzner RG, Mackall CL. Programming CAR-T cells to kill cancer. Nature biomedical engineering. 2018;2(6):377-91.
  10. Sadelain M, Brentjens R, Rivière I. The promise and potential pitfalls of chimeric antigen receptors. Current opinion in immunology. 2009;21(2):215-23.
  11. June CH, Sadelain M. Chimeric antigen receptor therapy. New England Journal of Medicine. 2018;379(1):64-73.
  12. Nicholson IC, Lenton KA, Little DJ, Decorso T, Lee FT, Scott AM, et al. Construction and characterisation of a functional CD19 specific single chain Fv fragment for immunotherapy of B lineage leukaemia and lymphoma. Molecular immunology. 1997;34(16-17):1157-65.
  13. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. New England Journal of Medicine. 2017;377(26):2531-44.
  14. Kato K, Makita S, Goto H, Kanda J, Fujii N, Shimada K, et al. Phase 2 study of axicabtagene ciloleucel in Japanese patients with relapsed or refractory large B-cell lymphoma. International Journal of Clinical Oncology. 2022;27(1):213-23.
  15. Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1–2 trial. The Lancet Oncology. 2019;20(1):31-42.
  16. Oluwole OO, Bouabdallah K, Muñoz J, De Guibert S, Vose JM, Bartlett NL, et al. Prophylactic corticosteroid use in patients receiving axicabtagene ciloleucel for large B-cell lymphoma. British Journal of Haematology. 2021;194(4):690-700.
  17. Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. New England Journal of Medicine. 2019;380(1):45-56.
  18. Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. New England Journal of Medicine. 2018;378(5):439-48.
  19. Goto H, Makita S, Kato K, Tokushige K, Fujita T, Akashi K, et al. Efficacy and safety of tisagenlecleucel in Japanese adult patients with relapsed/refractory diffuse large B-cell lymphoma. International Journal of Clinical Oncology. 2020;25(9):1736-43.
  20. Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. The Lancet. 2020;396(10254):839-52.
  21. Patrick DL, Powers A, Jun MP, Kim Y, Garcia J, Dehner C, et al. Effect of lisocabtagene maraleucel on HRQoL and symptom severity in relapsed/refractory large B-cell lymphoma. Blood Advances. 2021;5(8):2245-55.
  22. Singh N, Orlando E, Xu J, Xu J, Binder Z, Collins MA, et al., editors. Mechanisms of resistance to CAR T cell therapies. Seminars in cancer biology; 2020: Elsevier.
  23. Faramand R, Jain M, Staedtke V, Kotani H, Bai R, Reid K, et al. Tumor Microenvironment Composition and Severe Cytokine Release Syndrome (CRS) Influence Toxicity in Patients with Large B-Cell Lymphoma Treated with Axicabtagene Ciloleucel. Clinical Cancer Research. 2020;26(18):4823-31.
  24. Bonaldo G, Montanaro N, AlbertoVaccheri, Motola D. Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice. European Journal of Clinical Pharmacology. 2021;77(8):1225-34.
  25. Gust J, Annesley CE, Gardner RA, Bozarth X. EEG Correlates of Delirium in Children and Young Adults With CD19-Directed CAR T Cell Treatment-Related Neurotoxicity. Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society. 2021;38(2):135-42.
  26. van der Horst HJ, Nijhof IS, Mutis T, Chamuleau MED. Fc-Engineered Antibodies with Enhanced Fc-Effector Function for the Treatment of B-Cell Malignancies. Cancers (Basel). 2020;12(10).
  27. Bournazos S, Wang TT, Dahan R, Maamary J, Ravetch JV. Signaling by Antibodies: Recent Progress. Annu Rev Immunol. 2017;35:285-311.
  28. Swisher JF, Feldman GM. The many faces of FcγRI: implications for therapeutic antibody function. Immunol Rev. 2015;268(1):160-74.
  29. Kahl BS, Hamadani M, Radford J, Carlo-Stella C, Caimi P, Reid E, et al. A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. Clin Cancer Res. 2019;25(23):6986-94.
  30. Hartley JA, Flynn MJ, Bingham JP, Corbett S, Reinert H, Tiberghien A, et al. Pre-clinical pharmacology and mechanism of action of SG3199, the pyrrolobenzodiazepine (PBD) dimer warhead component of antibody-drug conjugate (ADC) payload tesirine. Sci Rep. 2018;8(1):10479.
  31. Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021;22(6):790-800.
  32. Salles G, Długosz-Danecka M, Ghesquières H, Jurczak W. Tafasitamab for the treatment of relapsed or refractory diffuse large B-cell lymphoma. Expert Opin Biol Ther. 2021;21(4):455-63.
  33. Jurczak W, Zinzani PL, Gaidano G, Goy A, Provencio M, Nagy Z, et al. Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. Ann Oncol. 2018;29(5):1266-72.
  34. Flowers CR, Leonard JP, Fowler NH. Lenalidomide in follicular lymphoma. Blood. 2020;135(24):2133-6.
  35. Lonial S, Jacobus S, Fonseca R, Weiss M, Kumar S, Orlowski RZ, et al. Randomized Trial of Lenalidomide Versus Observation in Smoldering Multiple Myeloma. J Clin Oncol. 2020;38(11):1126-37.
  36. Salles G, Duell J, González Barca E, Tournilhac O, Jurczak W, Liberati AM, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. Lancet Oncol. 2020;21(7):978-88.
  37. Klisovic RB, Leung WH, Brugger W, Dirnberger‐Hertweck M, Winderlich M, Ambarkhane SV, et al. A phase 2a, single‐arm, open‐label study of tafasitamab, a humanized, Fc‐modified, anti‐CD19 antibody, in patients with relapsed/refractory B‐precursor cell acute lymphoblastic leukemia. Cancer. 2021;127(22):4190-7.
  38. Salles G, Duell J, Barca EG, Tournilhac O, Jurczak W, Liberati AM, et al. Tafasitamab plus lenalidomide in relapsed or refractory diffuse large B-cell lymphoma (L-MIND): a multicentre, prospective, single-arm, phase 2 study. The Lancet Oncology. 2020;21(7):978-88.
  39. Topp MS, Gökbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. The Lancet Oncology. 2015;16(1):57-66.
  40. Kantarjian H, Stein A, Gökbuget N, Fielding AK, Schuh AC, Ribera J-M, et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. New England Journal of Medicine. 2017;376(9):836-47.
  41. Rambaldi A, Ribera JM, Kantarjian HM, Dombret H, Ottmann OG, Stein AS, et al. Blinatumomab compared with standard of care for the treatment of adult patients with relapsed/refractory Philadelphia chromosome–positive B‐precursor acute lymphoblastic leukemia. Cancer. 2020;126(2):304-10.
  42. Gökbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood, The Journal of the American Society of Hematology. 2018;131(14):1522-31.
  43. Hamers-Casterman C, Atarhouch T, Muyldermans S, Robinson G, Hamers C, Songa EB, et al. Naturally occurring antibodies devoid of light chains. Nature. 1993;363(6428):446-8.
  44. Chames P, Rothbauer U. Special Issue: Nanobody. Antibodies (Basel). 2020;9(1).
  45. Desmyter A, Decanniere K, Muyldermans S, Wyns L. Antigen specificity and high affinity binding provided by one single loop of a camel single-domain antibody. J Biol Chem. 2001;276(28):26285-90.
  46. Banihashemi SR, Hosseini AZ, Rahbarizadeh F, Ahmadvand D. Development of specific nanobodies (VHH) for CD19 immuno-targeting of human B-lymphocytes. Iran J Basic Med Sci. 2018;21(5):455-64.
  47. Wang H, Wang L, Li Y, Li G, Zhang X, Jiang D, et al. Nanobody-armed T cells endow CAR-T cells with cytotoxicity against lymphoma cells. Cancer Cell Int. 2021;21(1):450.
  48. Zhou Z, Han Y, Pan H-B, Sang C-J, Shi D-L, Feng C, et al. Tri-Specific CD19xCD20xCD22 VHH CAR-T Cells (LCAR-AIO) Eradicate Antigen-Heterogeneous B Cell Tumors, Enhance Expansion, and Prolong Persistence in Preclinical In Vivo Models. Blood. 2021;138(Supplement 1):1700-.
  49. Banihashemi SR, Rahbarizadeh F, Zavaran Hosseini A, Ahmadvand D, Khoshtinat Nikkhoi S. Liposome-based nanocarriers loaded with anthrax lethal factor and armed with anti-CD19 VHH for effectively inhibiting MAPK pathway in B cells. Int Immunopharmacol. 2021;100:107927.
  50. Delire B, Starkel P. The Ras/MAPK pathway and hepatocarcinoma: pathogenesis and therapeutic implications. Eur J Clin Invest. 2015;45(6):609-23.
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