Inibição da proteína PD-1 pelo método CRISPR-Cas9 como terapia antitumoral para tumores de pulmão de não pequenas células
DOI:
https://doi.org/10.23925/1984-4840.2019v21i1a2Palavras-chave:
carcinoma broncogênico, sistemas CRISPR-Cas, terapia genéticaResumo
O carcinoma de pulmão é o segundo tipo de tumor de maior incidência em todo o mundo, sendo 85% deles carcinomas de pulmão de não pequenas células (CPNPC). As células tumorais do CPNPC proliferam em razão de um bloqueio da resposta de linfócitos T citotóxicos. Na resposta imune a tumores, a interação do ligante-1 do receptor de morte celular programada (PD-L1), expresso em células tumorais com a proteína de morte celular programada 1 (PD-1), expressa em linfócitos T citotóxicos, promove a supressão da resposta imune, levando à inibição da ativação de linfócitos T citotóxicos. Apesar de as terapias biológicas mostrarem-se eficazes para o tratamento de tumores pulmonares, estudos buscam uma opção de tratamento genético, como o método CRISPR/Cas9. O objetivo desta revisão é fornecer uma atualização do método CRISPR-Cas9 e a aplicação dele como ferramenta terapêutica buscando desativar o gene que codifica a proteína PD-1 em casos de CPNPC. A alteração genética da proteína PD-1 pelo CRISPR-Cas9 pode interromper a interação entre receptor e ligante, permitindo que linfócitos T citotóxicos reconheçam e exerçam uma resposta antitumoral contra tumores de CPNPC.Downloads
Metrics
Referências
Nakamura H, Saji H. A worldwide trend of increasing primary adenocarcinoma of the lung. Surg Today. 2014;44(6):1004-12. https://doi.org/10.1007/s00595-013-0636-z
Garon EB. Current perspectives in immunotherapy for non-small cell lung cancer. Semin Oncol. 2015;42 Suppl 2:S11-8. https://doi.org/10.1053/j.seminoncol.2015.09.019
Herbst RS, Heymach JV, Lippman SM. Lung cancer. N Engl J Med. 2008;359(13):1367-80. https://doi.org/10.1056/NEJMra0802714
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11-30. https://doi.org/10.3322/caac.21166
Zer A, Leighl N. Promising targets and current clinical trials in metastatic non-squamous NSCLC. Front Oncol. 2014;4:329. https://doi.org/10.3389/fonc.2014.00329
Kim JW, Eder JP. Prospects for targeting PD-1 and PD‑L1 in various tumor types. Oncology (Williston Park). 2014;28 Suppl 3:15-28.
Sunshine J, Taube JM. PD-1/PD-L1 inhibitors. Curr Opin Pharmacol. 2015;23:32-8. https://doi.org/10.1016/j.coph.2015.05.011
Silva APS, Coelho PV, Anazetti M, Simioni PU. Targeted therapies for the treatment of non-small-cell lung cancer: monoclonal antibodies and biological inhibitors. Hum Vaccin Immunother. 2017;13(4):843‑53. https://doi.org/10.1080/21645515.2016.1249551
Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, et al. Phase I study of single‑agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: Safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28(19):3167-75. https://doi.org/10.1200/JCO.2009.26.7609
Akbay EA, Koyama S, Carretero J, Altabef A, Tchaicha JH, Christensen CL, et al. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov. 2013;3(12):1355-63. https://doi.org/10.1158/2159-8290.CD-13-0310
Kim JM, Chen DS. Immune escape to PD-L1/PD-1 blockade: seven steps to success (or failure). Ann Oncol. 2016;27(8):1492-504. https://doi.org/10.1093/annonc/mdw217
Makarova KS, Haft DH, Barrangou R, Brouns SJ, Charpentier E, Horvath P, et al. Evolution and classification of the CRISPR-Cas systems. Nat Rev Microbiol. 2011;9(6):467-77. https://doi.org/10.1038/nrmicro2577
Bondy-Denomy J, Garcia B, Strum S, Du M, Rollins MF, Hidalgo-Reyes Y, et al. Multiple mechanisms for CRISPR-Cas inhibition by anti-CRISPR proteins. Nature. 2015;526:136-9. https://doi.org/10.1038/nature15254
Richter C, Chang JT, Fineran PC. Function and regulation of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated (Cas) systems. Viruses. 2012;4(10):2291-311. https://doi.org/10.3390/v4102291
Cohen MH, Johnson JR, Chattopadhyay S, Tang S, Justice R, Sridhara R, et al. Approval summary: erlotinib maintenance therapy of advanced/metastatic non-small cell lung cancer (NSCLC). Oncologist. 2010;15(12):1344‑51. https://doi.org/10.1634/theoncologist.2010-0257
Carvalho L. Reclassifying bronchial-pulmonary carcinoma: differentiating histological type in biopsies by immunohistochemistry. Rev Port Pneumol. 2009;15(6):1101-19. https://doi.org/10.1016/S0873-2159(15)30195-1
Scagliotti GV, Hirsh V, Siena S, Henry DH, Woll PJ, Manegold C, et al. Overall survival improvement in patients with lung cancer and bone metastases treated with denosumab versus zoledronic acid: subgroup analysis from a randomized phase 3 study. J Thorac Oncol. 2012;7(12):1823-9. https://doi.org/10.1097/JTO.0b013e31826aec2b
Rossi A, Maione P, Bareschino MA, Schettino C, Sacco PC, Ferrara ML, et al. The emerging role of histology in the choice of first-line treatment of advanced non-small cell lung cancer: implication in the clinical decisionmaking. Curr Med Chem. 2010;17(11):1030-8. https://doi.org/10.2174/092986710790820589
Larsen JE, Minna JD. Molecular biology of lung cancer: clinical implications. Clin Chest Med. 2011;32(4):703-40.
Jančík S, Drábek J, Radzioch D, Hajdúch M. Clinical relevance of KRAS in human cancers. J Biomed Biotechnol. 2010; Article ID 150960:1-13. https://doi.org/10.1155/2010/150960
Duarte RLM, Paschoal MEM. Molecular markers in lung cancer: prognosis role and relationship to smoking. J Bras Pneumol. 2005;32(1):56-65. https://doi.org/10.1590/S1806-37132006000100012
Doebele RC, Oton AB, Peled N, Camidge DR, Bunn PA Jr. New strategies to overcome limitations of reversible EGFR tyrosine kinase inhibitor therapy in non-small cell lung cancer. Lung Cancer. 2010;69(1):1-12. https://doi.org/10.1016/j.lungcan.2009.12.009
Reungwetwattana T, Dy GK. Targeted therapiesin development for non-small cell lung cancer. J Carcinog. 2013;12:22. https://doi.org/10.4103/1477-3163.123972.eCollection 2013
Scaltriti M, Baselga J. The epidermal growth fator receptor pathway: a model for targeted therapy. Clin Cancer Res. 2006;12(18):5268-72. https://doi.org/10.1158/1078-0432.CCR-05-1554
Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit t cell responses. Immunity. 2007;27(1):111-22. https://doi.org/10.1016/j.immuni.2007.05.016
Sharpe AH, Wherry EJ, Ahmed R, Freeman GJ. The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat Immunol. 2007;8(3):239-45. https://doi.org/10.1038/ni1443
Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677-704. https://doi.org/10.1146/annurev.immunol.26.021607.090331
Francisco LM, Sage PT, Sharpe AH. The PD-1 pathway in tolerance and autoimmunity. Immunol Rev. 2010;236:219-42. https://doi.org/10.1111/j.1600-065X.2010.00923.x.
Jin HT, Ahmed R, Okazaki T. Role of PD-1 in regulating T-cell immunity. Curr Top Microbiol Immunol. 2011;350:17-37. https://doi.org/10.1007/82_2010_116
Ohaegbulam KC, Assal A, Lazar-Molnar E, Yao Y, Zang X. Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway. Trends Mol Med. 2015;21(1):24-33. https://doi.org/10.1016/j.molmed.2014.10.009
Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol. 2012;24(2):207-12. https://doi.org/10.1016/j.coi.2011.12.009
Gaj T, Gersbach CA, Barbas CF 3rd. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol. 2013;31(7):397-405. https://doi.org/10.1016/j.tibtech.2013.04.004
Gupta RM, Musunuru K. Expanding the genetic editing tool kit: ZFNs, TALENs, and CRISPR-Cas9. J Clin Invest. 2014;124(10):4154-61. https://doi.org/10.1172/JCI72992
Terns MP, Terns RM. CRISPR-based adaptive imune systems. Curr Opin Microbiol. 2011;14(3):321-7. https://doi.org/10.1016/j.mib.2011.03.005
Barrangou R, Marraffini LA. CRISPR-Cas systems: prokaryotes upgrade to adaptive immunity. Mol Cell. 2014;54(2):234-44. https://doi.org/10.1016/j.molcel.2014.03.011
Semenova E, Jore MM, Datsenko KA, Semenova A, Westra ER, Wanner B, et al. Interference by clustered regularly interspaced short palindromic repeat (CRISPR) RNA is governed by a seed sequence. Proc Natl Acad Sci. 2011;108(25):10098-103. https://doi.org/10.1073/pnas.1104144108
Reis A, Hornblower B; New England Biolabs. CRISPR/Cas9 and targeted genome editing: a new era in molecular biology. New Engl BioLabs [Internet]. 2014;1 [acessado em 07 mai. 2019]. Disponível em: https://www.neb.com/tools-and-resources/featurearticles/crispr-cas9-and-targetedgenome-editing-anew-era-in-molecular-biology
Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNAguided DNA endonuclease in adaptive bacterial immunity. Science. 2012;337(6096):816-21. https://doi.org/10.1126/science.1225829
Lin S, Staahl BT, Alla RK, Doudna JA. Enhanced homology-directed human genome engineering by controlled timing of CRISPR/Cas9 delivery. Elife. 2014;3:e04766. https://doi.org/10.7554/eLife.04766
Dance A. Core Concept: CRISPR gene editing. Proc Natl Acad Sci. 2015;112(20):6245-6. https://doi.org/10.1073/pnas.1503840112
Lin Y, Cradick TJ, Brown MT, Deshmukh H, Ranjan P, Sarode N, et al. CRISPR/Cas9 systems have off‑target activity with insertions or deletions between target DNA and guide RNA sequences. Nucleic Acids Res. 2014;42(11):7473-85. https://doi.org/10.1093/nar/gku402
Kim D, Bae S, Park J, Kim E, Kim S, Yu HR, et al. Digenome-seq: Genome-wide profiling of CRISPRCas9 off-target effects in human cells. Nat Methods. 2015;12(3):237-43. https://doi.org/10.1038/nmeth.3284
Torres-Ruiz R, Rodriguez-Perales S. CRISPR-Cas9: a revolutionary tool for cancer modelling. Int J Mol Sci. 2015;16(9):22151-68. https://doi.org/10.3390/ijms160922151
Kannan R, Ventura A. The CRISPR revolution and its impact on cancer research. Swiss Med Wkly. 2015;145:w14230. https://doi.org/10.4414/smw.2015.14230. eCollection 2015
Jena B, Dotti G, Cooper LJN. Redirecting T-cell specificity by introducing a tumor-specific chimeric antigen receptor. Blood. 2010;116(7):1035-44. https://doi.org/10.1182/blood-2010-01-043737
Sadelain M, Brentjens R, Rivière I. The basic principles of chimeric antigen receptor design. Cancer Discov. 2013;3(4):388-98. https://doi.org/10.1158/2159-8290.CD-12-0548
Ren J, Zhao Y. Advancing chimeric antigen receptor T cell therapy with CRISPR/Cas9. Protein Cell. 2017;8(9):634-43. https://doi.org/10.1007/s13238-017-0410-x
Su S, Hu B, Shao J, Shen B, Du J, Du Y, et al. CRISPR-Cas9 mediated efficient PD-1 disruption on human primary T cells from cancer patients. Sci Rep. 2016;6:20070. https://doi.org/10.1038/srep20070
Rupp LJ, Schumann K, Roybal KT, Gate RE, Ye CJ, Lim WA, et al. CRISPR/Cas9-mediated PD-1 disruption enhances anti-Tumor efficacy of human chimeric antigen receptor T cells. Sci Rep. 2017;7(1):737. https://doi.org/10.1038/s41598-017-00462-8.
Cyranoski D. CRISPR gene-editing tested in a person for the first time. Nature. 2016;539(7630):479. https://doi.org/10.1038/nature.2016.20988
Downloads
Publicado
Como Citar
Edição
Seção
Licença
Os autores no momento da submissão transferem os direitos autorais, assim, os manuscritos publicados passam a ser propriedade da revista.
O conteúdo do periódico está licenciado sob uma Licença Creative Commons 4.0, esta licença permite o livre acesso imediato ao trabalho e que qualquer usuário leia, baixe, copie, distribua, imprima, pesquise ou vincule aos textos completos dos artigos, rastreando-os para indexação, passá-los como dados para o software, ou usá-los para qualquer outra finalidade legal.