Novas perspectivas em imunoterapia: a importância das células dendríticas na imunoterapia alérgeno-específica
New perspectives in immunotherapy: the importance of dendritic cells in allergen-specific immunotherapy
Maria Angela Vigoritto; Gustavo Pradez
Resumo
A imunoterapia alérgeno-específica é o único tratamento capaz de alterar o curso natural da doença alérgica. Ensaios clínicos mostram que a imunoterapia é segura e eficaz para muitos pacientes. No entanto, ainda enfrenta problemas relacionados à eficácia, segurança, longa duração do tratamento e baixa adesão dos pacientes. Neste contexto, tem havido intensa pesquisa no desenvolvimento de adjuvantes com objetivo de aumentar a segurança, otimizar os esquemas de tratamento e melhorar a adesão dos pacientes. Alérgenos foram modificados (glicoconjugados) com carboidratos derivados de Saccharomyces cerevisae para aumentar sua captação e apresentação através dos receptores de carboidratos presentes nas células dendríticas, beneficiando-se da capacidade de atuarem na indução de tolerância para iniciar respostas imunes. À luz de novas evidências, essas células constituem alvo terapêutico chave para se obter uma resposta adequada à imunoterapia alérgeno-específica, com potencial de contribuição na inovação do campo da Imunoterapia.
Palavras-chave
Abstract
Allergen-specific immunotherapy is the only treatment capable of altering the natural course of allergic disease. Clinical trials have shown that immunotherapy is safe and effective for many patients. However, it still faces problems related to efficacy, safety, long treatment duration and poor patient compliance. In this context, there has been intense research into the development of adjuvant treatments that increase safety, optimize treatment regimens, and improve patient compliance. Allergens were modified (glycoconjugated) with carbohydrates derived from Saccharomyces cerevisae to increase their uptake and presentation through carbohydrate receptors in dendritic cells, benefiting from their ability to induce tolerance and initiate immune response. In light of the new evidence, these cells are a key therapeutic target for adequate response to allergenspecific immunotherapy and can drive innovation in the field of immunotherapy.
Keywords
Referências
1. JutelM, AgacheI, BoniniS, BurksAW, CalderonM, Canonica W, et al. International Consensuson Allergen Immunotherapy II: mechanisms, standardization, and pharmacoeconomics. J Allergy Clin Immunol. 2016;137:358-68.
2. Pfaar O, Bonini S, Cardona V, Demoly P, Jakob T, Jutel M, et al. Perspectives in allergen immunotherapy: 2017 and beyond. Allergy. 2018;73(Suppl104):5-23.
3. Kucuksezer UC, Ozdemir C, Cevhertas L, Ogulur I, Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy and allergen tolerance. Allergol Int. 2020 Oct;69(4):549-60. doi: 10.1016/j.alit.2020.08.002.
4. Durham SR, Till SJ. Immunologic changes associated with allergen immunotherapy. J Allergy Clin Immunol. 1998;102:157-64.
5. Pereira VAR, Aun WCT, Mello JF. Mecanismos da imunoterapia alérgeno-específica. Arq Asma Alerg Imunol. 2017;1(3):257-62.
6. Schülke S, Vieths S. Dendritic cell targeting with C-type lectins for improvement of allergen immunotherapy. J Allergy Clin Immunol. 2016 Aug;138(2):568-70.
7. Pfaar O, Creticos PS, Kleine-Tebbe J, Canonica GW, Palomares O, Schülke S. One Hundred Ten Years of Allergen Immunotherapy: A Broad Look Into the Future. J Allergy Clin Immunol Pract. 2021 May;9(5):1791-803. doi: 10.1016/j.jaip.2020.12.067. Erratum in: J Allergy Clin Immunol Pract. 2021 Oct;9(10):3851. PMID: 33966868.
8. Komlósi ZI, Kovács N, Sokolowska M, van de Veen W, Akdis M, Akdis CA. Highlights of Novel Vaccination Strategies in Allergen Immunotherapy. Immunol Allergy Clin North Am. 2020 Feb;40(1):15- 24. doi: 10.1016/j.iac.2019.09.010.
9. Sheng KC, Pouniotis DS, Wright MD, Tang CK, Lazoura E, Pietersz GA, et al. Mannan derivatives induce phenotypic and functional maturation of mouse dendritic cells. Immunology. 2006 Jul;118(3):372-83. doi: 10.1111/j.1365-2567.2006.02384.x.
10. Tada H, Nemoto E, Shimauchi H, Watanabe T, Mikami T, Matsumoto T, et al. Saccharomyces cerevisiae- and Candida albicans-derived mannan induced production of tumor necrosis factor alpha by human monocytes in a CD14- and Toll-like receptor 4-dependent manner. Microbiol Immunol. 2002;46(7):503-12.
11. Weinberger EE, Himly M, Myschik J, Hauser M, Altmann F, Isakovic A, et al. Generation of hypoallergenic neoglycoconjugates for dendritic cell targeted vaccination: a novel tool for specific immunotherapy. J Control Release. 2013 Jan 28;165(2):101-9.
12. Manzano AI, Javier Cañada F, Cases B, Sirvent S, Soria I, Palomares O, et al. Structural studies of novel glycoconjugates from polymerized allergens (allergoids) and mannans as allergy vaccines. Glycoconj J. 2016 Feb;33(1):93-101. doi: 10.1007/s10719-015-9640-4.
13. Bona C, Bot A. The 2011 Nobel Prize - honoring the memory of Dr. Ralph Steinman. Int Rev Immunol. 2011 Oct-Dec;30(5-6):233-4. doi: 10.3109/08830185.2011.630972.
14. Sirvent S, Soria I, Cirauqui C, Cases B, Manzano AI, Diez-Rivero CM, et al. Novel vaccines targeting dendritic cells by coupling allergoids to nonoxidized mannan enhance allergen uptake and induce functional regulatory T cells through programmed death ligand 1. J Allergy Clin Immunol. 2016 Aug;138(2):558-67.e11
15. Benito-Villalvilla C, Soria I, Subiza JL, Palomares O. Novel vaccines targeting dendritic cells by coupling allergoids to mannan. Allergo J Int. 2018;27(8):256-262. doi: 10.1007/s40629-018-0069-8.
16. Benito-Villalvilla C, Soria I, Pérez-Diego M, Fernández-Caldas E, Subiza JL, Palomares O. Alum impairs tolerogenic properties induced by allergoid-mannan conjugates inhibiting mTOR and metabolic reprogramming in human DCs. Allergy. 2020 Mar;75(3):648-659. doi: 10.1111/all.14036.
17. Oliveira CH, Binotti RS. Uso de polissacarídeos em esquemas de imunoterapia. Rev bras alerg imunopatol. 2002;25(6):200-3.
18. Benito-Villalvilla C, Pérez-Diego M, Angelina A, Kisand K, Rebane A, Subiza JL, et al. Allergoid-mannan conjugates reprogram monocytes into tolerogenic dendritic cells via epigenetic and metabolic rewiring. J Allergy Clin Immunol. 2022 Jan;149(1):212-22.e9. doi: 10.1016/j.jaci.2021.06.012.
Submetido em:
10/08/2022
Aceito em:
19/09/2022
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