Novas Estratégias em Imunoterapia com Células CAR-T em Pacientes com Leucemia Linfoblástica Aguda: Investigando a Ascensão da Terapêutica
DOI:
https://doi.org/10.32635/2176-9745.RBC.2025v71n3.5017Palavras-chave:
Receptores de Antígenos Quiméricos, Imunoterapia, Técnicas Imunológicas, Leucemia-Linfoma Linfoblástico de Células Precursoras, Engenharia GenéticaResumo
Introdução: A leucemia linfoide aguda (LLA) é uma neoplasia hematológica identificada pela proliferação descontrolada de linfoblastos mutados de linhagem B e/ou T, que compromete gravemente o organismo humano e apresenta alta taxa de letalidade. Esse quadro conduz os pacientes a um percurso clínico extenuante, agravado pelos efeitos adversos das terapias convencionais. Nesse contexto, a estratégia de tratamento com células T modificadas geneticamente para expressar o receptor de antígeno quimérico (CAR) demonstra eficácia significativa, superando as adversidades dessa patologia agressiva. Objetivo: Analisar as implicações clínicas identificadas nos principais estudos sobre tratamento com células CAR-T no tratamento da LLA. Método: Revisão bibliográfica integrativa que envolve coleta de artigos científicos de bases de dados como PubMed, SciELO, Periódicos, Scopus, Web of Science e J-STAGE a partir do ano 2000, com foco em investigar, analisar e destacar os impactos da terapia com células CAR-T nos pacientes com LLA. Resultados: Os dados evidenciam que, apesar dos obstáculos decorrentes dos efeitos adversos e da resistência tumoral, o uso de células CAR-T é uma abordagem terapêutica essencial no combate à LLA, apresentando altos índices de remissão e sobrevida global, observados nos testes clínicos. No entanto, a terapia apresenta empecilhos consideráveis, incluindo custos elevados, desafios na garantia de qualidade de produção e altas taxas de recidiva, comprometendo a validação definitiva da eficácia e segurança. Conclusão: É imprescindível a realização de novas pesquisas para aprimorar a construção do CAR-T e a identificação de biomarcadores mais precisos.
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Referências
Sheykhhasan M, Manoochehri H, Dama P. Use of CAR T-cell for acute lymphoblastic leukemia (ALL) treatment: a review study. Cancer Gene Ther. 2022;(29):1080-96. doi: https://doi.org/10.1038/s41417-021-00418-1 DOI: https://doi.org/10.1038/s41417-021-00418-1
Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017;7:e577. doi: https://doi.org/10.1038/bcj.2017.53 DOI: https://doi.org/10.1038/bcj.2017.53
Aureli A, Marziani B, Venditti A, et al. Acute lymphoblastic leukemia immunotherapy treatment: now, next, and beyond. Cancers. 2023;15(13):3346. doi: https://doi.org/10.3390/cancers15133346 DOI: https://doi.org/10.3390/cancers15133346
Chen Z, Xin Q, Wei W, et al. The pathogenesis and development of targeted drugs in acute T lymphoblastic leukaemia. Br J Pharmacol. 2023;180(8):1017-37. doi: https://doi.org/10.1111/bph.16029 DOI: https://doi.org/10.1111/bph.16029
Huang F-L, Liao E-C, Li C-L, et al. Pathogenesis of pediatric B‑cell acute lymphoblastic leukemia: molecular pathways and disease treatments (review). Oncol Lett. 2020;20(1):448-54. doi: https://doi.org/10.3892/ol.2020.11583 DOI: https://doi.org/10.3892/ol.2020.11583
Zuckerman T, Rowe JM. Pathogenesis and prognostication in acute lymphoblastic leukemia. F1000Prime Rep. 2014;6:59. doi: https://doi.org/10.12703/p6-59 DOI: https://doi.org/10.12703/P6-59
Yoon J-H, Lee S. Diagnostic and therapeutic advances in adults with acute lymphoblastic leukemia in the era of gene analysis and targeted immunotherapy. Korean J Intern Med. 2024;39(1):34-56. doi: https://doi.org/10.3904/kjim.2023.407 DOI: https://doi.org/10.3904/kjim.2023.407
Kansal R. Diagnosis and molecular pathology of lymphoblastic leukemias and lymphomas in the era of genomics and precision medicine: historical evolution and current concepts-part 2: B-/TCell acute lymphoblastic leukemias. Lymphatics. 2023;1(2):118-54. doi: https://doi.org/10.3390/lymphatics1020011 DOI: https://doi.org/10.3390/lymphatics1020011
Liu Y, Easton J, Shao Y, et al. The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia. Nat Genet. 2017;49:1211-8. doi: https://doi.org/10.1038/ng.3909 DOI: https://doi.org/10.1038/ng.3909
Liu S, Deng B, Yin Z, et al. Combination of CD19 and CD22 CAR-T cell therapy in relapsed B-cell acute lymphoblastic leukemia after allogeneic transplantation. Am J Hematol. 2021;96:671-9. doi: https://doi.org/10.1002/ajh.26160 DOI: https://doi.org/10.1002/ajh.26160
AlMoshary M, Altahan SM, Alswayyed AF. Early response and outcomes of bone marrow to chemotherapy in T-cell acute lymphoblastic leukemia. Pak J Med Sci. 2024;40(5):979-84. doi: https://doi.org/10.12669/pjms.40.5.7584 DOI: https://doi.org/10.12669/pjms.40.5.7584
Dourthe ME, Baruchel A. CAR T-cells for T-cell acute lymphoblastic leukemia. EJC Paediatr Oncol. 2024;3:100150. doi: https://doi.org/10.1016/j.ejcped.2024.100150 DOI: https://doi.org/10.1016/j.ejcped.2024.100150
Campos-Sanchez E, Toboso-Navasa A, Romero-Camarero I, et al. Acute lymphoblastic leukemia anddevelopmental biology: a crucial interrelationship. Cell Cycle. 2011;10(20):3473-86. doi: https://doi.org/10.4161/cc.10.20.11979 DOI: https://doi.org/10.4161/cc.10.20.17779
Coccaro N, Anelli L, Zagaria A, et al. Next-generation sequencing in acute lymphoblastic leukemia. Int J Mol Sci. 2019;20(12):2929. doi: https://doi.org/10.3390/ijms20122929 DOI: https://doi.org/10.3390/ijms20122929
Comeaux EQ, Mullighan CG. TP53 Mutations in hypodiploid acute lymphoblastic leukemia. Cold Spring Harb Perspect Med. 2017;7(3):a026286. doi: https://doi.org/10.1101/cshperspect.a026286 DOI: https://doi.org/10.1101/cshperspect.a026286
Jing J, Ma Y, Xie Z, et al. Acute T-cell lymphoblastic leukemia: chimeric antigen receptor technology may offer a new hope. Front Immunol. 2024;15:1410519. doi: https://doi.org/10.3389/fimmu.2024.1410519 DOI: https://doi.org/10.3389/fimmu.2024.1410519
Patel J, Gao X, Wang H. An update on clinical trials and potential therapeutic strategies in T-cell acute lymphoblastic leukemia. Int J Mol Sci. 2023;24(8):7201. doi: https://doi.org/10.3390/ijms24087201 DOI: https://doi.org/10.3390/ijms24087201
Tomasik J, Jasiński M, Basak GW. Next generations of CAR-T cells - new therapeutic opportunities in hematology? Front Immunol. 2022;13:1034707. doi: https://doi.org/10.3389/fimmu.2022.1034707 DOI: https://doi.org/10.3389/fimmu.2022.1034707
Pan J Cordo V, van der Zwet JCG, Canté-Barrett K, et al. T-cell acute lymphoblastic leukemia: a roadmap to targeted therapies. Blood Cancer Discov. 2020;2(1):19-31. doi: https://doi.org/10.1158/2643-3230.BCD-20-0093 DOI: https://doi.org/10.1158/2643-3230.BCD-20-0093
Tan Y, Shan L, Zhao L, et al. Long-term follow-up of donorderived CD7 CAR T-cell therapy in patients with T-cell acute lymphoblastic leukemia. J Hematol Oncol. 2023;16(34):1-15. doi: https://doi.org/10.1186/s13045-023-01427-3 DOI: https://doi.org/10.1186/s13045-023-01427-3
Araújo LGL, Rodrigues VP, Silva MML, et al. Perfil demográfico e clínico de casos de neoplasias hematológicas em crianças e adolescentes. Rev Bras Cancerol. 2022;68(2):e-242356. doi: https://doi.org/10.32635/2176-9745.RBC.2022v68n2.2356 DOI: https://doi.org/10.32635/2176-9745.RBC.2022v68n2.2356
Agência Nacional de Vigilância Sanitária [Internet]. Brasília, DF: Anvisa; 2022. Anvisa aprova 3º produto de terapia avançada para tratamento do câncer, 2022 out 26. [acesso 2025 maio 15]. Disponível em: https://www.gov.br/anvisa/pt-br/assuntos/noticias-anvisa/2022/anvisa-aprova-3o-produto-de-terapia-avancada-paratratamento-do-cancer
Agência Nacional de Vigilância Sanitária [Internet]. Brasília, DF: Anvisa; 2022. Anvisa aprova mais um produto de terapia avançada para tratamento de câncer no Brasil, 2023 dez 29. [acesso 2025 maio 15]. Disponível em: https://www.gov.br/anvisa/pt-br/assuntos/noticias-anvisa/2023/anvisa-aprova-maisum-produto-de-terapia-avancada-para-tratamento-docancer-no-brasil
Agência Nacional de Vigilância Sanitária [Internet]. Brasília, DF: Anvisa; 2022. Anvisa aprova produto de terapia avançada para tratamento de câncer, 2022 fev 23. [acesso 2025 maio 15]. Disponível em: https://www.gov.br/anvisa/pt-br/assuntos/noticias-anvisa/2022/anvisa-aprova-produto-de-terapia-avancada-paratratamento-de-cancer
Agência Nacional de Vigilância Sanitária [Internet]. Brasília, DF: Anvisa; 2022. Anvisa aprova registro de produto de terapia avançada para câncer, 2022 abr 1. [acesso 2025 maio 15]. Disponível em: https://www.gov.br/anvisa/pt-br/assuntos/noticias-anvisa/2022/anvisa-aprova-registro-de-produto-de-terapia-avancadapara-cancer
Agência Nacional de Vigilância Sanitária [Internet]. Brasília, DF: Anvisa; 2022. Autorizada pesquisa nacional com células CAR-T para tratar câncer, 2022 jul 13. [acesso 2025 maio 15]. Disponível em: https://www.gov.br/anvisa/pt-br/assuntos/noticias-anvisa/2022/autorizada-pesquisa-nacional-com-celulas-car-t-paratratar-cancer-1
Bhattarai N. Assessing immunogenicity of products for gene therapy and t cell therapy [Internet]. [Sem local]: FDA; 2017. [acesso 2025 maio 15]. Disponível em: https://www.fda.gov/vaccines-blood-biologics/biologics-research-projects/assessing-immunogenicityproducts-gene-therapy-and-t-cell-therapy
Food and Drug Administration [Internet]. Silver Spring: FDA; 2017. FDA approval brings first gene therapy to the United States. [acesso 2025 maio 15]. Disponível em: https://www.fda.gov/news-events/press-announcements/fda-approval-brings-first-genetherapy-united-states
Food and Drug Administration [Internet]. Silver Spring: FDA; 2017. FDA approves tisagenlecleucel for B-cell ALL and tocilizumab for cytokine release syndrome. [acesso 2025 maio 15]. Disponível em: https://www.fda.gov/drugs/resources-information-approved-drugs/fdaapproves-tisagenlecleucel-B-cell-all-and-tocilizumabcytokine-release-syndrome
Ministério da Saúde (BR). Ministério da Saúde. Portaria Conjunta nº 21, de 10 de dezembro de 2021. Aprova as Diretrizes Diagnósticas e Terapêuticas – Mesilato de Imatinibe no Tratamento da Leucemia Linfoblástica Aguda Cromossoma Philadelphia Positivo do Adulto. Diário Oficial da União, Brasília, DF. 10 dez 2021; Edição 234;Seção 1:111.
Pan K, Farrukh H, Chittepu VCSR, et al. CAR race to cancer immunotherapy: from CAR T, CAR NK to CAR macrophage therapy. J Exp Clin Cancer Res. 2022;41:119. doi: https://doi.org/10.1186/s13046-022-02327-z DOI: https://doi.org/10.1186/s13046-022-02327-z
American Cancer Society [Internet]. Atlanta: ACS; ©2025. Acute lymphocytic leukemia (ALL) subtypes and prognostic factor, 2018 out 17. [Acesso 2025 maio 15]. Disponível em: https://www.cancer.org/cancer/types/acute-lymphocytic-leukemia/detection-diagnosisstaging/how-classified.html
National Cancer Institute [Internet]. Bethesda: National Cancer Institute; 2024. Acute Lymphoblastic Leukemia Treatment (PDQ)–Patient Version. [Acesso 2025 maio 15]. Disponível em: https://www.cancer.gov/types/leukemia/patient/adult-all-treatment-pdq
Chen Y-J, Abila B, Mostafa Kamel Y. CAR-T: what is next? Cancers. 2023;15(3):663. doi: https://doi.org/10.3390/cancers15030663 DOI: https://doi.org/10.3390/cancers15030663
Alnefaie A, Albogami S, Asiri Y, et al. Chimeric antigen receptor T-cells: an overview of concepts, applications, limitations, and proposed solutions. Front. Bioeng. Biotechnol. 2022;10:797440. doi: https://doi.org/10.3389/fbioe.2022.797440 DOI: https://doi.org/10.3389/fbioe.2022.797440
Ren A, Tong X, Xu N, et al. CAR T-cell immunotherapy treating T-ALL: challenges and opportunities. Vaccines. 2023;11(1):165. doi: https://doi.org/10.3390/vaccines11010165 DOI: https://doi.org/10.3390/vaccines11010165
Mohanty R, Chowdhury CR, Arega S, et al. CAR T cell therapy: a new era for cancer treatment (Review). Oncology Reports. 2019;42(6):2183-95. doi: https://doi.org/10.3892/or.2019.7335 DOI: https://doi.org/10.3892/or.2019.7335
Boyiadzis MM, Dhodapkar MV, Brentjens RJ, et al. Chimeric antigen receptor (CAR) T therapies for the treatment of hematologic malignancies: clinical perspective and significance. J Immunother Cancer. 2018;6(1):137. doi: https://doi.org/10.1186/s40425-018-0460-5 DOI: https://doi.org/10.1186/s40425-018-0460-5
Li YR, Lyu Z, Chen Y, et al. Frontiers in CAR-T cell therapy for autoimmune diseases. Trends Pharmacol Sci. 2024;45(9):839-57. doi: https://doi.org/10.1016/j.tips.2024.07.005 DOI: https://doi.org/10.1016/j.tips.2024.07.005
National Cancer Institute [Internet]. Washington: NCI; [sem data]. CAR T cells: engineering patients´ immune cells to treat their cancers, 2025 fev 26. [acesso 2025 mar 10]. Disponível em: https://www.cancer.gov/aboutcancer/treatment/research/car-t-cells
Weber F, Carrijo MF, Pereira Érica R, et al. Tratamento da leucemia linfóide aguda em crianças: uma revisão narrativa. Braz J Develop. 2023;9(4):13353-69. doi: https://doi.org/10.34117/bjdv9n4-054 DOI: https://doi.org/10.34117/bjdv9n4-054
Park CH. Making potent CAR T Cells using genetic engineering and synergistic agents. Cancers. 2021;13(13):3236. doi: https://doi.org/10.3390/cancers13133236 DOI: https://doi.org/10.3390/cancers13133236
Wei J, Han X, Bo J, et al. Target selection for CAR-T therapy. J Hematol Oncol. 2019;12(62):1-9. doi: https://doi.org/10.1186/s13045-019-0758-x DOI: https://doi.org/10.1186/s13045-019-0758-x
Iriguchi S, Kaneko S. Toward the development of true “off-the-shelf ” synthetic T-cell immunotherapy. Cancer Science. 2019;110(1):16-22. doi: https://doi.org/10.1111/cas.13892 DOI: https://doi.org/10.1111/cas.13892
Liu J, Jiang P, Lu Z, et al. Decoding leukemia at the single-cell level: clonal architecture, classification, microenvironment, and drug resistance. Exp Hematol. 2024;13(1):12. doi: https://doi.org/10.1186/s40164-024-00479-6 DOI: https://doi.org/10.1186/s40164-024-00479-6
M.D. Anderson Cancer Center Maryland: NIH; ©2025. Umbilical & cord blood (CB) derived CARengineered NK cells for B lymphoid malignancies. ClinicalTrials.gov [Internet]. 2024 [acesso 2025 mar 25]. Disponível em: https://clinicaltrials.gov/study/NCT03056339
Magnani CF, Gaipa G, Lussana F, et al. Sleeping beauty-engineered CAR T cells achieve antileukemic activity without severe toxicities. J Clin Invest. 2020;130(11):6021-33. doi: https://doi.org/10.1172/JCI138473 DOI: https://doi.org/10.1172/JCI138473
Newman H, Teachey DT. A bright horizon: immunotherapy for pediatric T-Cell malignancies. Int J Mol Sci. 2022;23(15):8600. doi: https://doi.org/10.3390/ijms23158600 DOI: https://doi.org/10.3390/ijms23158600
Sánchez-Martínez D, Baroni ML, Gutierrez-Agüera F, et al. Fratricide-resistant CD1a-specific CAR T cells for the treatment of cortical T-cell acute lymphoblastic leukemia. Blood. 2019;133(21):2291-304. doi: https://doi.org/10.1182/blood-2018-10-882944 DOI: https://doi.org/10.1182/blood-2018-10-882944
Pan J, Tan Y, Deng B, et al. Previous-transplant or new-match donor CD5 CAR T cells in pediatric and adult relapsed/refractory T-ALL: first-in-human, phase 1 study [Internet]. In: 29º Congress of the European Hematology Association (EHA); 2024 Jun 13-16; Madrid: EHA Library; 2024.
Sasine J. Feasibility and safety of collecting and combining autologous hematopoietic stem cells with chimeric antigen receptor (CAR) T-cell therapy in subjects with relapsed/refractory hematological malignancies [Internet]. ClinicalTrials.gov. 2025 [acesso 2024 abr. 2]. Disponível em: https://clinicaltrials.gov/study/NCT05887167
Xu X, Sun Q, Liang X, et al. Mechanisms of relapse after CD19 CAR T-cell therapy for acute lymphoblastic leukemia and its prevention and treatment strategies. Front Immunol. 2019;10:2664. doi: https://doi.org/10.3389/fimmu.2019.02664 DOI: https://doi.org/10.3389/fimmu.2019.02664
Zhang P, Meng J, Li Y, et al. Nanotechnology-enhanced immunotherapy for metastatic cancer. Innovation (Camb Mass). 2021;2(4):100174. doi: https://doi.org/10.1016/j.xinn.2021.100174 DOI: https://doi.org/10.1016/j.xinn.2021.100174
Zhang Y, Chen H, Song Y, et al. CAR T-cell therapy as a bridge to hematopoietic stem cell transplantation for refractory/relapsed B-cell acute lymphoblastic leukemia. Br J Haematol. 2020;189(1):146-52. doi: https://doi.org/10.1111/bjh.16339 DOI: https://doi.org/10.1111/bjh.16339
Zhang Y, Li C, Du M, et al. Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies. Blood Cancer J. 2023;13(1):61. doi: https://doi.org/10.1038/s41408-023-00822-w DOI: https://doi.org/10.1038/s41408-023-00822-w
Zheng R, Zhu X, Xiao Y. Advances in CAR-T-cell therapy in T-cell malignancies. J Hematol Oncol. 2024;17(1):49. doi: https://doi.org/10.1186/s13045- 024-01568-z DOI: https://doi.org/10.1186/s13045-024-01568-z
Iriguchi S, Yasui Y, Kawai Y, et al. A clinically applicable and scalable method to regenerate T-cells from iPSCs for off-the-shelf T-cell immunotherapy. Nat Commun. 2021;12(430):1-15. doi: https://doi.org/10.1038/s41467-020-20658-3 DOI: https://doi.org/10.1038/s41467-020-20658-3
Moradi S, Mahdizadeh H, Šarić T, et al. Research and therapy with induced pluripotent stem cells (iPSCs): social, legal, and ethical considerations. Stem Cell Res Ther; 2019;10(1):341. doi: https://doi.org/10.1186/s13287-019-1455-y DOI: https://doi.org/10.1186/s13287-019-1455-y
Ceppi F, Wilson AL, Annesley C, et al. Modified manufacturing process modulates CD19CAR T-cell engraftment fitness and leukemia-free survival in pediatric and young adult subjects. Cancer Immunol Res. 2022;10(7):856-70. doi: https://doi.org/10.1158/2326-6066.CIR-21-0501 DOI: https://doi.org/10.1158/2326-6066.CIR-21-0501
Whittemore R, Knafl K. The integrative review: updated methodology. J Adv Nurs. 2005;52(5):546-53. doi: https://doi.org/10.1111/j.1365-2648.2005.03621.x DOI: https://doi.org/10.1111/j.1365-2648.2005.03621.x
Oermann MH, Knafl KA. Strategies for completing a successful integrative review. Nurse Author Ed. 2021;31(3-4):65-68. doi: https://doi.org/10.1111/nae2.30 DOI: https://doi.org/10.1111/nae2.30
Slim K, Nini E, Forestier D, et al. Methodological index for non-randomized studies (MINORS): development and validation of a new instrument. ANZ J Surg. 2003;73(9):712-6. https://doi.org/10.1046/j.1445-2197.2003.02748.x DOI: https://doi.org/10.1046/j.1445-2197.2003.02748.x
Ma LL, Wang YY, Yang ZH, et al. Methodological quality (risk of bias) assessment tools for primary and secondary medical studies: what are they and which is better? Mil Med Res. 2020;7(7):1-11. doi: https://doi.org/10.1186/s40779-020-00238-8 DOI: https://doi.org/10.1186/s40779-020-00238-8
Celgene. A study to evaluate the safety and efficacy of JCAR017 in pediatric subjects with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and B-cell non-Hodgkin lymphoma (B-NHL). ClinicalTrials.gov [Internet]. 2024 [acesso 2025 mar 15]. Disponivel em: https://clinicaltrials.gov/ct2/show/NCT03743246
Kite A Gilead Company. A study evaluating the safety and efficacy of brexucabtagene autoleucel (KTE-X19) in adult subjects with relapsed/refractory B-precursor acute lymphoblastic leukemia (ZUMA-3). ClinicalTrials.gov [Internet]. [acesso 2025 mar 18]. Disponivel em: https://clinicaltrials.gov/ct2/show/NCT02614066
Chiesa R, Georgiadis C, Syed F, et al. Base-edited CAR7 T Cells for relapsed T-cell acute lymphoblastic leukemia. N Engl J Med. 2023;389(10):899-910. doi: https://doi.org/10.1056/nejmoa2300709 DOI: https://doi.org/10.1056/NEJMoa2300709
St. Jude Children’s Research Hospital. CAR T-cell therapy directed to CD70 for pediatric patients with hematological malignancies. ClinicalTrials.gov [Internet]. 2025 [acesso 2025 jun 19]. Disponível em: https://clinicaltrials.gov/study/NCT06326463
The Affiliated Hospital of Xuzhou Medical University. Clinical study of anti-CD1a CAR-T in the treatment of R/R acute T-lymphoblastic leukemia/lymphoblastic lymphoma. ClinicalTrials.gov [Internet]. 2023 [acesso 2023 fev 27]. Disponível em: https://clinicaltrials.gov/study/NCT05745181
Essen Biotech. Sequential CAR-T cells therapy for CD5/CD7 positive T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma using CD5/CD7-specific CAR-T cells (BAH246). ClinicalTrials.gov [Internet]. 2024 [acesso 2025 mar 1]. Disponivel em: https://clinicaltrials.gov/study/NCT06420076
M. D. Anderson Cancer Center. Phase I/II study of CD5 CAR engineered IL15-transduced cord bloodderived NK cells in conjunction with lymphodepleting chemotherapy for the management of relapsed/ refractory hematological malignances. ClinicalTrials.gov [Internet]. 2025 [acesso 2025 jun 1]. Disponível em: https://clinicaltrials.gov/study/NCT05110742 72. The Affiliated People’s Hospital of Ningbo University. Study of CAR-T cell therapy in the treatment of relapsed/ refractory hematological malignancies. ClinicalTrials.gov [Internet]. 2022 [acesso 2025 mar 6]. Disponível em: https://clinicaltrials.gov/study/NCT05528887 73.
Fondazione Matilde Tettamanti Menotti De Marchi Onlus. Transposon-manipulated allogeneic CARCIKCD19 cells in pediatric and adult patients with r/r ALL post HSCT (CARCIK). ClinicalTrials.gov [Internet]. 2023 [atualizado 2025 maio 6]. Disponível em: https://clinicaltrials.gov/study/NCT03389035
Seattle Children’s Hospital. A pediatric and young adult trial of genetically modified T cells directed against CD19 for relapsed/refractory CD19+ leukemia. ClinicalTrials.gov [Internet]. 2024 [acesso 2025 maio 26]. Disponível em: https://clinicaltrials.gov/study/NCT02028455
Ghorashian S, Lucchini G, Richardson R, et al. CD19/ CD22 targeting with cotransduced CAR T cells to prevent antigen-negative relapse after CAR T-cell therapy for B-cell ALL. Blood. 2024;143(2):118-23. doi: https://doi.org/10.1182/blood.2023020621 DOI: https://doi.org/10.1182/blood.2023020621
Cao XY, Zhang JP, Zhao YL, et al. Analysis benefits of a second Allo-HSCT after CAR-T cell therapy in patients with relapsed/refractory B-cell acute lymphoblastic leukemia who relapsed after transplant. Front. Immunol. 2023;14:1191382. doi: https://doi.org/10.3389/fimmu.2023.1191382 DOI: https://doi.org/10.3389/fimmu.2023.1191382
Mazinani M, Rahbarizadeh F. CAR-T cell potency: from structural elements to vector backbone components. Biomark Res. 2022;10(70):1-24. doi: https://doi.org/10.1186/s40364-022-00417-w DOI: https://doi.org/10.1186/s40364-022-00417-w
Xu J, Luo W, Li C, et al. Targeting CD22 for B-cell hematologic malignancies. Exp Hematol Oncol. 2023;12(1):90. doi: https://doi.org/10.1186/s40164-023-00454-7 DOI: https://doi.org/10.1186/s40164-023-00454-7
Cordoba S, Onuoha S, Thomas S. et al. CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial. Nat Med. 2021;27:1797-805. doi: https://doi.org/10.1038/s41591-021-01497-1 DOI: https://doi.org/10.1038/s41591-021-01497-1
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