Review: Single Chain Fragment Variable sebagai Pemandu Diagnosis dan Terapi Bertarget Human Epidermal Growth Factor Receptor 2 Kanker Payudara
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Abstract
Single chain fragment variable (scFv) merupakan antibodi rekombinan yang terdiri dari bagian fragmen antigen-binding (Fab) antibodi dengan ukuran sangat kecil sekitar 26 -27 kDa. Secara umum scFv bersifat stabil ,dikode oleh satu gen sehingga akan mempermudah modifikasi genetik. Dibandingkan dengan antibodi lengkap, scFv yang memiliki aktivitas pengikatan antigen yang serupa memiliki kelebihan lain diantaranya adalah ukurannya yang kecil, penetrasi ke pembuluh darah dan jaringan yang lebih baik, serta imunogenisitas yang lebih rendah. Oleh karena itu, scFv memiliki potensi yang sangat baik untuk digunakan sebagai senyawa pemandu diagnosis maupun terapi penyakit. Hasil dari berbagai penelitian menunjukkan scFv anti-HER2 (Human Epidermal Growth Factor Receptor 2) dapat digunakan sebagai pemandu pada diagnosis kanker payudara HER2+ baik menggunakan Magnetic Resonance Imaging (MRI) ataupun positron-emission tomography (PET). Pada terapi kanker payudara bertarget reseptor HER2, scFv anti HER2 juga memiliki potensi digunakan sebagai pemandu untuk imunotoksin, antibody drug conjugate (ADC), prodrug, dan pretargeted radioimmunotherapy (PRIT).
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References
. Globocan. Indonesian Fact Data Sheet [Internet]. 2020 [cited 2022 May 18]. Available from: https://gco.iarc.fr/today/data/factsheets/populations/360-indonesia-fact-sheets.pdf
. Harbeck N, Gnant M. Breast cancer. Lancet. 2017;389(10074):1134–50. https://doi.org/10.1016/S0140-6736(16)31891-8
. Arteaga CL, Engelman JA. ERBB receptors: From oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell. 2014;25(3):282–303. https://doi.org/10.1016/J.CCR.2014.02.025
. Chung A, Cui X, Audeh W, Giuliano A. Current status of anti-her2 therapies: predicting and overcoming herceptin resistance. 2013; https://doi.org/10.1016/j.clbc.2013.04.001
. Merry CR, McMahon S, Forrest ME, Bartels CF, Saiakhova A, Bartel CA, et al. Transcriptome-wide identification of mRNAs and lincRNAs associated with trastuzumab-resistance in HER2-positive breast cancer. Oncotarget. 2016;7(33):53230–44. https://doi.org/10.18632/ONCOTARGET.10637
. Chiu ML, Goulet DR, Teplyakov A, Gilliland GL. Antibody Structure and Function: The Basis for Engineering Therapeutics. Antibodies 2019, Vol 8, Page 55. 2019;8(4):55. https://doi.org/10.3390/ANTIB8040055
. Satheeshkumar PK. Expression of Single Chain Variable Fragment (scFv) Molecules in Plants: A Comprehensive Update. Mol Biotechnol. 2020;62(3):151–67. https://doi.org/10.1007/S12033-020-00241-3/FIGURES/4
. Grilo AL, Mantalaris A. The Increasingly Human and Profitable Monoclonal Antibody Market. Trends Biotechnol. 2019;37(1):9–16. https://doi.org/10.1016/J.TIBTECH.2018.05.014
. Kang TH, Jung ST. Reprogramming the Constant Region of Immunoglobulin G Subclasses for Enhanced Therapeutic Potency against Cancer. Biomolecules. 2020;10(3). https://doi.org/10.3390/BIOM10030382
. Chen F, Ma K, Madajewski B, Zhuang L, Zhang L, Rickert K, et al. Ultrasmall targeted nanoparticles with engineered antibody fragments for imaging detection of HER2-overexpressing breast cancer. Nat Commun 2018 91. 2018;9(1):1–11. https://doi.org/10.1038/S41467-018-06271-5
. Ulaner GA, Hyman DM, Ross DS, Corben A, Chandarlapaty S, Goldfarb S, et al. Detection of HER2-Positive Metastases in Patients with HER2-Negative Primary Breast Cancer Using 89Zr-Trastuzumab PET/CT. J Nucl Med. 2016;57(10):1523–8. https://doi.org/10.2967/JNUMED.115.172031
. Laforest R, Lapi SE, Oyama R, Bose R, Tabchy A, Marquez-Nostra B V., et al. [89Zr]Trastuzumab: Evaluation of Radiation Dosimetry, Safety, and Optimal Imaging Parameters in Women with HER2-Positive Breast Cancer. Mol Imaging Biol 2016 186. 2016;18(6):952–9. https://doi.org/10.1007/S11307-016-0951-Z
. Ueda M, Hisada H, Temma T, Shimizu Y, Kimura H, Ono M, et al. Gallium-68-Labeled Anti-HER2 Single-Chain Fv Fragment: Development and In Vivo Monitoring of HER2 Expression. Mol Imaging Biol. 2015;17(1):102–10. https://doi.org/10.1007/S11307-014-0769-5/FIGURES/4
. Alric C, Hervé-Aubert K, Aubrey N, Melouk S, Lajoie L, Même W, et al. Targeting HER2-breast tumors with scFv-decorated bimodal nanoprobes. J Nanobiotechnology. 2018;16(1). https://doi.org/10.1186/S12951-018-0341-6
. Ding N, Sano K, Kanazaki K, Ohashi M, Deguchi J, Kanada Y, et al. In Vivo HER2-Targeted Magnetic Resonance Tumor Imaging Using Iron Oxide Nanoparticles Conjugated with Anti-HER2 Fragment Antibody. Mol Imaging Biol 2016 186. 2016;18(6):870–6. https://doi.org/10.1007/S11307-016-0977-2
. Allahyari H, Heidari S, Ghamgosha M, Saffarian P, Amani J. Immunotoxin: A new tool for cancer therapy. Tumor Biol. 2017;39(2):1–11. https://doi.org/10.1177/1010428317692226
. Raja SM, Desale SS, Mohapatra B, Luan H, Soni K, Zhang J, et al. Marked enhancement of lysosomal targeting and efficacy of ErbB2-targeted drug delivery by HSP90 inhibition. Oncotarget. 2016;7(9):10522. https://doi.org/10.18632/ONCOTARGET.7231
. Vafadar A, Taheri-Anganeh M, Jamali Z. In Silico Design and Evaluation of scFv-CdtB as a Novel Immunotoxin for Breast Cancer Treatment Analysis of Suitable Signal Peptides for Designing a Secretory Thermostable Cyanide Degrading Nitrilase: An in Silico Approach View project Methotrexate View p. Artic Int J Cancer Manag. 2020; https://doi.org/10.5812/ijcm.96094
. Lee S, Park S, Nguyen MT, Lee E, Kim J, Baek S, et al. A chemical conjugate between HER2-targeting antibody fragment and Pseudomonas exotoxin A fragment demonstrates cytotoxic effects on HER2-expressing breast cancer cells. BMB Rep. 2019;52(8):496–501. https://doi.org/10.5483/BMBREP.2019.52.8.250
. Goleij Z, Mahmoodzadeh Hosseini H, Sedighian H, Behzadi E, Halabian R, Sorouri R, et al. Breast cancer targeted/ therapeutic with double and triple fusion Immunotoxins. J Steroid Biochem Mol Biol. 2020;200:105651. https://doi.org/10.1016/j.jsbmb.2020.105651
. Zhang H, Wang Y, Wu Y, Jiang X, Tao Y, Yao Y, et al. Therapeutic potential of an anti-HER2 single chain antibody–DM1 conjugates for the treatment of HER2-positive cancer. Signal Transduct Target Ther 2017 21. 2017;2(1):1–11. https://doi.org/10.1038/SIGTRANS.2017.15
. Ogitani Y, Hagihara K, Oitate M, Naito H, Agatsuma T. Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody–drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity. Cancer Sci. 2016;107(7):1039–46. https://doi.org/10.1111/CAS.12966
. Jiang K, Li J, Yin J, Ma Q, Yan B, Zhang X, et al. Targeted delivery of CXCR4-siRNA by scFv for HER2(+) breast cancer therapy. Biomaterials. 2015;59:77–87. https://doi.org/10.1016/J.BIOMATERIALS.2015.04.030
. Lu D, Guo Y, Hu Y, Wang M, Li C, Gangrade A, et al. Fusion of apoptosis-related protein Cytochrome c with anti-HER-2 single-chain antibody targets the suppression of HER-2+ breast cancer. J Cell Mol Med. 2021;25:10638–49. https://doi.org/10.1111/jcmm.17001
. Zhang H, Lam L, Nagai Y, Zhu Z, Chen X, Ji MQ, et al. A targeted immunotherapy approach for HER2/neu transformed tumors by coupling an engineered effector domain with interferon-γ. Oncoimmunology. 2018;7(4):e1300739. https://doi.org/10.1080/2162402X.2017.1300739
. Wang J-H, Forterre A V, Zhao J, Frimannsson DO, Delcayre A, Antes TJ, et al. Anti-HER2 scFv-Directed Extracellular Vesicle-Mediated mRNA-Based Gene Delivery Inhibits Growth of HER2-Positive Human Breast Tumor Xenografts by Prodrug Activation. Mol Cancer Ther. 2018;17(5):1133–42. https://doi.org/10.1158/1535-7163.MCT-17-0827
. Yoon S, Kim YH, Kang SH, Kim SK, Lee HK, Kim H, et al. Bispecific Her2 × cotinine antibody in combination with cotinine-(histidine)2-iodine for the pre-targeting of Her2-positive breast cancer xenografts. J Cancer Res Clin Oncol. 2014;140(2):227–33. https://doi.org/10.1007/S00432-013-1548-4/FIGURES/5