Nanoantibodies applications in medicine
DOI:
https://doi.org/10.30827/ars.v63i2.22199Keywords:
antibodies, nanoantibodies, neoplasms, hepatitis, Alzheimer disease, Parkinson, diarrhea, SARS-CoV-2Abstract
Introduction: Nanoantibodies are composed solely of the variable region of the heavy chain and are obtained from some species of camelids and sharks. They have high binding capacity, high specificity, small size, high accessibility, and high tissue penetration, so they could potentially be used to treat, diagnose, and prevent several diseases.
Method: A bibliographic review of the medical applications of nanoantibodies was carried out. Scientific articles were examined, published in English and Spanish from 2015 to 2021 in Google Academic, Elsevier, PubMed, Clinical trials, Annual Reviews, and ScienceDirect databases. Studies that showed greater value according to language, information accuracy, and publication date were preferred.
Results and discussion: 21 articles were selected to be evaluated and analyzed, of which 20 were preclinical studies and one clinical study. Nanoantibodies stand out as therapeutic, diagnostic, and preventive alternatives against cancer, hepatitis C, Alzheimer’s disease, Parkinson’s disease, diarrhea caused by rotavirus, and COVID-19.
Conclusions: Nanoantibodies can be very useful for the prevention, diagnosis, and treatment of different diseases; however, it is necessary to continue developing clinical and preclinical studies that support the safety and efficacy of these drugs.
Downloads
References
Hameed A. Conventional and Nano- Antibodies and Their Future Uses. AAJMS. 2019;2(3):14-34.
Langjahr P, Sotelo P. Presente y futuro de los anticuerpos recombinantes terapéuticos. Mem Inst Investig Cienc Salud. 2016;14(2):110-21.
Abbas A, Lichtman A, Pillai S. Antigen Recognition in the Adaptive Immune System: Structure of Lymphocyte Antigen Receptors and Development of Immune Repertoires. En: Basic Immunology: Functions and Disorders of the Immune System [Internet]. 6ª ed. 2020. Disponible en: https://www-clinicalkey-com.ezproxy.sibdi.ucr.ac.cr/#!/content/book/3-s2.0-B9780323549431000040?scrollTo=%23hl0000384
Wong A, Sykora C, Rogers L, Higginbotham J, Wang J. Modified Nanoantibodies Increase Sensitivity in Avidin-Biotin Immunohistochemistry. Appl Immunohistochem Mol Morphol. 2018;26(9):682-8.
Li T, Vandesquille M, Koukouli F, Dudeffant C, Youssef I, Lenormand P, et al. Camelid single-domain antibodies: A versatile tool for in vivo imaging of extracellular and intracellular brain targets. J Controlled Release. 2016;243:1-10.
Liu W, Song H, Chen Q, Yu J, Xian M, Nian R, et al. Recent advances in the selection and identification of antigen-specific nanobodies. Mol Immunol. 2018;96:37-47.
Vázquez V. Análisis transcriptómico y desarrollo de una biblioteca de los genes codificantes para anticuerpos IgNAR del tiburón Heterodontus francisci. Baja California, México: Centro de Investigación Científica y de Educación Superior de Ensenada; 2018.
English H, Hong J, Ho M. Ancient species offers contemporary therapeutics: an update on shark VNAR single domain antibody sequences, phage libraries and potential clinical applications. 2020. Doi:10.1093/abt/tbaa001
Pedreáñez A, Mosquera J, Muñoz N, Tene D. Nanoanticuerpos: pequeñas moléculas, grandes posibilidades. Acta Bioclinica. 2021;11(22):296-319. Doi:0.6084/m9.figshare.14200553.
Parreno G, Vega C, Bok M, Adúriz M, Aguilar A. Nanoanticuerpos derivados de llamas: una alternativa innovadora para controlar las diarreas por rotavirus y norovirus humano. ANMAT. 2019;26-30.
Li C, Tang Z, Hu Z, Wang Y, Yang X, Mo F, et al. Natural Single-Domain Antibody-Nanobody: A Novel Concept in the Antibody Field. J Biomed Nanotechnol.2018;14(1):1-19.
Chen J, He Q, Xu Y, Fu J, Li Y, Tu Z, et al. Nanobody medicated immunoassay for ultrasensitive detection of cancer biomarker alpha-fetoprotein. Talanta. 2016;147:523-30. Doi: 10.1016/j.talanta.2015.10.027.
Van Impe K, Bethuyne J, Cool S, Impens F, Ruano-Gallego D, De Wever O, et al. A nanobody targeting the F-actin capping protein CapG restrains breast cancer metastasis. Breast Cancer Res BCR. 2013;15(6):R116. Doi: 10.1186/bcr3585.
Heukers R, Fan TS, Wit RH de, Senten JR van, Groof TWM de, Bebelman MP, et al. The constitutive activity of the virally encoded chemokine receptor US28 accelerates glioblastoma growth. Oncogene. 2018(30):1-12. Doi: 10.1038/s41388-018-0255-7.
Henan Cancer Hospital. Clinical Study of CD19/CD20 Bispecific Nanobody-derived CAR-T Cells in Refractroy/Relasped B Cell Lymphoma [Internet]. clinicaltrials.gov. 2019. Report No.: NCT03881761.
Jittavisutthikul S, Thanongsaksrikul J, Thueng-In K, Chulanetra M, Srimanote P, Seesuay W, et al. Humanized-VHH transbodies that inhibit HCV protease and replication. Viruses. 2015;7(4):2030-56.Doi: 10.3390/v7042030.
Vandesquille M, Li T, Po C, Ganneau C, Lenormand P, Dudeffant C, et al. Chemically-defined camelid antibody bioconjugate for the magnetic resonance imaging of Alzheimer’s disease. mAbs. 2017;9(6):1016-27.
Dorresteijn B, Rotman M, Faber D, Schravesande R, Suidgeest E, Weerd L van der, et al. Camelid heavy chain only antibody fragment domain against β-site of amyloid precursor protein cleaving enzyme 1 inhibits β-secretase activity in vitro and in vivo. FEBS J. 2015;282(18):3618-31.
Rincon M, Zhou L, Marneffe C, Voytyuk I, Wouters Y, Dewilde M, et al. AAV mediated delivery of a novel anti-BACE1 VHH reduces Abeta in an Alzheimer’s disease mouse model. bioRxiv. 2019;1-22.
Butler DC, Joshi SN, Genst ED, Baghel AS, Dobson CM, Messer A. Bifunctional Anti-Non-Amyloid Component α-Synuclein Nanobodies Are Protective In Situ. PLOS ONE. 2016;11(11):e0165964. Doi: 10.1371/journal.pone.0165964.
Iljina M, Hong L, Horrocks MH, Ludtmann MH, Choi ML, Hughes CD, et al. Nanobodies raised against monomeric ɑ-synuclein inhibit fibril formation and destabilize toxic oligomeric species. BMC Biol. 2017;15:57. Doi: 10.1186/s12915-017-0390-6.
Chatterjee D, Bhatt M, Butler D, De Genst E, Dobson CM, Messer A, et al. Proteasome-targeted nanobodies alleviate pathology and functional decline in an α-synuclein-based Parkinson’s disease model. Npj Park Di. 2018;4(1):1-10. Doi: 10.1038/s41531-018-0062-4.
Maffey L. Prevención y tratamiento de Rotavirus A mediante nanoanticuerpos VHH anti-VP6 [Tesis doctoral]. Buenos Aires: Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires; 2016.
Mendez, M. Vinculación, transferencia y utilidad social de los conocimientos : el caso de INCUINTA (2004-2019) [Tesis de grado]. Universidad Nacional de La Plata: Memoria Académica; 2021.
Crowell L, Goodwine C, Holt C, Rocha L, Vega C, Rodriguez S, et al. Development of a platform process for the production and purification of single-domain antibodies. Biotechnol Bioeng. 2021;118(9):3348-3358. Doi: 10.1002/bit.27724.
Amcheslavsky A, Wallace A, Ejemel M, Li Q, McMahon C, Stoppato M, et al. Anti-CfaE nanobodies provide broad cross-protection against major pathogenic enterotoxigenic Escherichia coli strains, with implications for vaccine design. Sci Rep. 2021;11(1):2751. Doi: 10.1038/s41598-021-81895-0.
Esperbent, C. Construyen una biblioteca de nanoanticuerpos de llamas contra la COVID-19. Revista de Investigaciones Agropecuarias. 2020;46(2):145-7.
Zhou Z, Wang X, Zhang X, Zhang Y, et al. Significance of neutralizing antibodies in COVID-19 therapy: progress and prospect. J Chin Pharm Sci. 2021;30(2):87-106. Doi: 10.5246/jcps.2021.02.008.
Hasson S, Al-Jabri A. Immunized camels and COVID-19. Asian Pac J Trop Med. 2020;13(6):239-241. Doi: 10.4103/1995-7645.282561.
Djemli S, Tahraoui A, Boussena M, Rouag F, et al. Camelid Antibodies May well be effective Against SARS-CoV-2 variants. 2021;6(6):604-606.
Sánchez C. Conociendo y comprendiendo la célula cancerosa: Fisiopatología del cáncer. Rev Médica Clínica Las Condes. 2013;24(4):553-62. Doi: 10.1016/S0716-8640(13)70659-X.
Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57-70. Doi: 10.1016/s0092-8674(00)81683-9.
Mitrus I, Bryndza E, Sochanik A, Szala S. Evolving models of tumor origin and progression. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2012;33(4):911-7. Doi: 10.1007/s13277-012-0389-0.
Van Audenhove I, Gettemans J. Nanobodies as Versatile Tools to Understand, Diagnose, Visualize and Treat Cancer. EBioMedicine. 2016;8:40-8. Doi: 10.1016/j.ebiom.2016.04.028.
Nikooharf A, Arezumand R, Mansouri K, Khoshi AH, Namdar Ahmadabad H. Development of a Recombinant Monospecific Anti-PLGF Bivalent Nanobody and Evaluation of it in Angiogenesis Modulation. Mol Biotechnol. 2020;62(11-12):580-8. Doi: 10.1007/s12033-020-00275-7.
Jiménez A. Virtual biopsy: seeing invisible cancer. SEBBM. 2018. Doi: 10.18567/sebbmdiv_ANC.2018.01.1.
Arezumand R, Alibakhshi A, Ranjbari J, Ramazani A, Muyldermans S. Nanobodies As Novel Agents for Targeting Angiogenesis in Solid Cancers. Front Immunol. 2017;0. Doi: 10.3389/fimmu.2017.01746.
Verhaar ER, Woodham AW, Ploegh HL. Nanobodies in cancer. Semin Immunol. 2020;101425. Doi: 10.1016/j.smim.2020.101425.
Guidotti LG, Chisari FV. Immunobiology and pathogenesis of viral hepatitis. Annu Rev Pathol Mech Dis. 2006;1(1):23-61. Doi: 10.1146/annurev.pathol.1.110304.100230.
Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med. 2004;350(11):1118-29. Doi: 10.1056/NEJMra031087.
Ferrari C, Missale G, Boni C, Urbani S. Immunopathogenesis of hepatitis B. J Hepatol. 2003;39 Suppl 1:S36-42. Doi: 10.1016/s0168-8278(03)00137-5.
Pawlotsky J-M. Pathophysiology of hepatitis C virus infection and related liver disease. Trends Microbiol. 2004;12(2):96-102. Doi: 10.1016/j.tim.2003.12.005.
Rius S, Tormos AM, Pérez S, Taléns R. Vascular pathology: Cause or effect in Alzheimer disease?. Neurol Engl Ed. 2018;33(2):112-20. Doi: 10.1016/j.nrl.2015.07.010.
Apostolova L. Alzheimer Disease. Contin Lifelong Learn Neurol. 2016;22(2):419-34. Doi: 10.1212/CON.0000000000000307.
Asefy Z, Hoseinnejhad S, Ceferov Z. Nanoparticles approaches in neurodegenerative diseases diagnosis and treatment. Neurol Sci. 2021;42(7):2653-60. Doi: 10.1007/s10072-021-05234-x.
Marín M DS, Carmona V H, Ibarra Q M, Gámez C M, Marín M DS, Carmona V H, et al. Enfermedad de Parkinson: fisiopatología, diagnóstico y tratamiento. Rev Univ Ind Santander Salud. 2018;50(1):79-92. Doi: 10.18273/revsal.v50n1-2018008.
Vázquez GE, Zoghbi HY. Parkinson’s Disease Genetics and Pathophysiology. Annu Rev Neurosci. 2021;44(1):87-108. Doi: 10.1146/annurev-neuro-100720-034518.
DeMaagd G, Philip A. Parkinson’s Disease and Its Management. Pharm Ther. 2015;40(8):504-32.
de Lau LML, Breteler MMB. Epidemiology of Parkinson’s disease. Lancet Neurol. 2006;5(6):525-35. Doi: 10.1016/S1474-4422(06)70471-9.
Michel PP, Hirsch EC, Hunot S. Understanding Dopaminergic Cell Death Pathways in Parkinson Disease. Neuron. 2016;90(4):675-91.Doi: 10.1016/j.neuron.2016.03.038.
α-Synuclein Promotes SNARE-Complex Assembly in Vivo and in Vitro | Science. 2010. doi: 10.1126/science.1195227.
Giasson BI, Murray IVJ, Trojanowski JQ, Lee VM-Y. A Hydrophobic Stretch of 12 Amino Acid Residues in the Middle of α-Synuclein Is Essential for Filament Assembly *. J Biol Chem. 2001;276(4):2380-6. Doi: 10.1074/jbc.M008919200.
Múñez E, Pintos I, Ramos A. Protocolo diagnóstico y tratamiento de la diarrea en el paciente inmunocomprometido. Med - Programa Form Médica Contin Acreditado. 2018;12(55):3285-3288. Doi: 10.1016/j.med.2018.04.017.
Barraca J. Protocolo diagnóstico de la diarrea crónica. Med - Programa Form Médica Contin Acreditado.2016;12(4):197-202. Doi: 10.1016/j.med.2016.02.013.
Arco R, Lázaro J, Díaz P. Protocolo diagnóstico y terapéutico de la diarrea aguda. Med - Programa Form Médica Contin Acreditado. 2019;12(87):5135-9. Doi: 10.1016/j.med.2019.10.007.
Escribano L, Rodríguez A, Centeno G. Protocolo diagnóstico etiopatogénico de la diarrea crónica. Med - Programa Form Médica Contin Acreditado. 2020;13(1):38-44. Doi: 10.1016/j.med.2020.01.005.
Fei P, Chen J, Jiang Y, Bai H, et al. Rotavirus-Induced Diarrhea Changes the Proteins, Amino Acids and Fatty Acids Profiles in Fecal Samples of the Infants. Iran J Pediatr. 2021;31(1). Doi: 10.5812/ijp.100031.
Maffey L, Vega CG, Parreño V, Garaicoechea L. Controlling Rotavirus-associated diarrhea: Could single-domain antibody fragments make the difference? Rev Argent Microbiol. 2015;47(4):368-79. Doi: 10.1016/j.ram.2015.09.005.
Fernandes C, Pereira S, Luiz M, Zuliani J, Furtado G, Stabeli R. Camelid Single-Domain Antibodies As an Alternative to Overcome Challenges Related to the Prevention, Detection, and Control of Neglected Tropical Diseases. Front Immunol. 2017;8:653. Doi: 10.3389/fimmu.2017.00653.
Pérez M, Gómez J, Dieguez R. Características clínico-epidemiológicas de la COVID-19. Rev habanera cienc médi. 2020;19 (2):1-15.
Serra M. COVID-19. De la patogenia a la elevada mortalidad en el adulto mayor y con comorbilidades. Rev habanera cienc médi. 2021;19(3).
Avila J. Coronavirus COVID-19; patogenia, prevención y tratamiento. 4ed. Lejona: salusplay; 2020. 19-25 p.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2022 Celeste Ortega-Monge, Noelia Arce-Rodríguez, Maripaz Santamaría-Muñoz, Marianela Chavarría-Rojas, María Fernanda Rojas Salas, Eleaneth Baltodano Viales, German L Madrigal Redondo
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The articles, which are published in this journal, are subject to the following terms in relation to the rights of patrimonial or exploitation:
- The authors will keep their copyright and guarantee to the journal the right of first publication of their work, which will be distributed with a Creative Commons BY-NC-SA 4.0 license that allows third parties to reuse the work whenever its author, quote the original source and do not make commercial use of it.
b. The authors may adopt other non-exclusive licensing agreements for the distribution of the published version of the work (e.g., deposit it in an institutional telematic file or publish it in a monographic volume) provided that the original source of its publication is indicated.
c. Authors are allowed and advised to disseminate their work through the Internet (e.g. in institutional repositories or on their website) before and during the submission process, which can produce interesting exchanges and increase citations of the published work. (See The effect of open access).
