Palabras clave
Linfocitos T
Ingeniería genética
Inmunoterapia adoptiva
Neoplasias
Protocolos antineoplásicos
Pediatría
Cómo citar
Resumen
El cáncer en niños y adolescentes comprende un grupo heterogéneo de neoplasias. Dentro de estas, la leucemia es la más frecuente. Actualmente, la inmunoterapia con anticuerpos monoclonales y la terapia celular adoptiva basada en la modificación por medio de ingeniería genética de las células T representa una gran oportunidad para los pacientes que no responden a las terapias convencionales. Una de las inmunoterapias aprobadas por agencias reguladoras europeas y estadounidenses que ha mostrado seguridad y eficacia son las células T modificadas con receptores quiméricos de antígeno que reconocen el antígeno CD19 en pacientes con leucemia linfoblástica aguda. Asimismo, la terapia ha demostrado ser exitosa en pacientes pediátricos con leucemia linfoblástica aguda B refractaria o en segunda recaída. Esta revisión describe la ingeniería genética para la generación de las células T modificadas con receptores quiméricos de antígeno, sus aplicaciones clínicas y la efectividad de los ensayos clínicos actuales en pacientes pediátricos.
Referencias
Johnston, WT. Erdmann F, Newton R, Steliarova Foucher E, Schüz J, Roman E. Childhood cancer: Estimating regional and global incidence. Cancer Epidemiol. 2021;71(Pt B):101662.
Schüz J, Roman E. Childhood cancer: A global perspective. Cancer Epidemiol. 2021;71(Pt B):101878.
Lewandowska A, Zych B, Papp K, Zrubcová D, Kadučáková H, Šupínová M, et al. Problems, Stressors and Needs of Children and Adolescents with Cancer. Children (Basel). 2021;8(12):1173.
Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17-48.
Instituto Nacional de Salud [Internet]. Bogotá: Ministerio de Salud y Protección Social. Boletínes Epidemiológicos. Disponible en: https://www.ins.gov.co/buscador-eventos/Paginas/Vista Boletin Epidemilogico.aspx
Manrique Hernández EF, Rojas Díaz MP, Rodriguez Villamizar LA. Clustering of non leukemia childhood cancer in Colombia: a nationwide study. F1000Res. 2021;10:86.
Lam CG, Howard SC, Bouffet E, Pritchard-Jones K. Science and health for all children with cancer. Science. 2019;363(6432):1182-1186.
Erdmann F, Frederiksen LE, Bonaventure A, Mader L, Hasle H, Robinson LL, et al. Childhood cancer: Survival, treatment modalities, late effects and improvements over time. Cancer Epidemiol. 2020;71(Pt B):101733.
Bhakta N, Force LM, Allemani C, Atun R, Bray F, Coleman MP, et al. Childhood cancer burden: a review of global estimates. Lancet Oncol. 2019;20(1):42-53.
Binnewies M, Roberts EW, Kersten K, Chan V, Fearon DF, Merand M, et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med. 2018;24:541-550.
Kimpo MS, Oh B, Lee S. The Role of Natural Killer Cells as a Platform for Immunotherapy in Pediatric Cancers. Curr Oncol Rep. 2019;21(10):93.
Zoine JT, MooreSE, Velasquez MP. Leukemia’s Next Top Model? Syngeneic Models to Advance Adoptive Cellular Therapy. Front. inmunol. 2022;13:867103.
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017;377(26):2531-2544.
Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia. Engl J Med. 2014;371(16):1507-1517.
Boettcher M, Joechner A, Li Z, Yang SF, Schlegel P. Development of CAR T Cell Therapy in Children-A Comprehensive Overview. J Clin Med. 2022;11(8):2158.
Gardner R, Finney O, Annesley C, Brakke H, Summers C, Leger K, et al. Intent to treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood. 2017;129(25):3322-3331.
Oiseth SJ, Aziz MS. Cancer immunotherapy: a brief review of the history, possibilities, and challenges ahead. J Cancer Metastasis Treat. 2017;3:250-61.
Dobosz P, Dzieciątkowski T. The Intriguing History of Cancer Immunotherapy. Front Immunol. 2019;10:2965.
Parish CR. Cancer immunotherapy: The past, the present and the future. Immunol Cell Biol. 2003;81:106-113.
Burnet FM. Production of Antibodies. BMJ. 1942;1:417-418.
Kaur K, Khatik GL. Cancer Immunotherapy: An Effective Tool in Cancer Control and Treatment. Curr Cancer Ther Rev. 2020;16(1):62-69.
Phan TG, Long GV, Scolyer RA. Checkpoint inhibitors for cancer immunotherapy. Multiple checkpoints on the long road towards cancer immunotherapy. Immunol Cell Biol. 2015;93(4):323-5.
Hurst JH. Cancer immunotherapy innovator James Allison receives the 2015 Lasker~DeBakey Clinical Medical Research Award. J Clin Invest. 2015;125(10):3732-3736
Allison JP, Mclntyre Bw, Bloch D. Tumor specificn antigen of murine T-lymphoma defined with monoclonal antibody. J Immunol. 1982;129(5):2293-300.
Eno J. Immunotherapy Through the Years. J Adv Pract Oncol. 2017;8(7):747-753.
Choudhry H, Helmi N, Abdulaal WH, Zeyadi M, Zamzami MA, Wu W, et al. Prospects of IL-2 in Cancer Immunotherapy. Biomed Res Int. 2018:1-7.
Boon T, Cerottini JC, Van den Eynde B, Van der Bruggen P, Van Pel A. Tumor antigens recognized by T lymphocytes. Annu Rev Immunol. 1994;12:337-65.
Löffler A, Kufer P, Lutterbüse R, Zettl F, Daniel PT, Schwenkenbecher JM, et al. A recombinant bispecific single-chain antibody, CD19 x CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes. Blood. 2000; 95(6):2098-103.
Dana H, Chalbatani GM, Jalali SA, Mirzaei HR, Grupp SA, Suarez ER, et al. CAR-T cells: Early successes in blood cancer and challenges in solid tumors. Acta Pharm Sin B. 2021;11(5):1129-1147.
Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541(7637):321-330.
Loose D, Van de Wiele C. The immune system and cancer. Cancer Biother Radiopharm. 2009;24(3):369-76.
Ribas A. Adaptive Immune Resistance: How Cancer Protects from Immune Attack. Cancer Discov. 2015;5(9): 915–919.
Miliotou AN, Papadopoulou LC. CAR T-cell Therapy: A New Era in Cancer Immunotherapy. Curr Pharm Biotechnol. 2018;19(1): 5–18.
Dunn GP, Old LJ, Schreiber RD. The Immunobiology of Cancer Immunosurveillance and Immunoediting. Immunity. 2004;21(2):137– 148.
Koebel CM, Vermi W, Swann JB, Zerafa N, Rodig SJ, Old LJ, et al. Adaptive immunity maintains occult cancer in an equilibrium state. Nature. 2007;450(7171): 903–907.
Tang S, Ning Q, Yang L, Mo Z, Tang S. Mechanisms of immune escape in the cancer immune cycle. Int Immunopharmacol. 2020;86:106700.
Beatty GL, Gladney WL. Immune Escape Mechanisms as a Guide for Cancer Immunotherapy. Clin Cancer Res. 2015;21(4): 687–692.
Tomasi TB, Magner WJ, Khan AN. Epigenetic regulation of immune escape genes in cancer. Cancer Immunol Immunother. 2006;55(10): 1159–1184.
Mohanty R, Chowdhury CR, Arega S, Sen P, Ganguly P, Ganguly N. CAR T cell therapy: A new era for cancer treatment (Review). Oncol Rep. 2019;42(6): 2183–2195.
De la Roche M, Asano Y, Griffiths GM. Origins of the cytolytic synapse. Nat Rev Immunol. 2016 Jul;16(7):421-32.
Wang Z, Wu Z, Liu Y, Han W. New development in CAR-T cell therapy. J Hematol Oncol. 2017;10(1):53.
Eshhar Z, Waks T, Gross G, Schindler DG. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci U S A. 1993;90(2):720-724.
Brocker T, Karjalainen K. Signals through T cell receptor-zeta chain alone are insufficient to prime resting T lymphocytes. J Exp Med. 1995;181(5):1653-1659.
Zhao Z, Chen Y, Francisco NM, Zhang Y, Wu M. The application of CAR-T cell therapy in hematological malignancies: advantages and challenges. Acta Pharm Sin B. 2018;8(4):539-551.
Finney HM, Lawson AD, Bebbington CR, Weir AN. Chimeric receptors providing both primary and costimulatory signaling in T cells from a single gene product. J Immunol. 1998;161(6):2791-2797.
Zhang C, Liu J, Zhong JF, Zhang X. Engineering CAR-T cells. Biomark Res. 2017;5:22.
Chmielewski M, Abken H. TRUCKs: the fourth generation of CARs. Expert Opin Biol Ther. 2015;15(8):1145-1154.
Stancovski I, Schindler DG, Waks T, Yarden Y, Sela M, Eshhar Z. Targeting of T lymphocytes to Neu/HER2-meric single chain Fv receptors. J Immunol. 1993;151(11):6577–6582.
Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018;378(5):439–448.
Jiang T, Zhou C, Ren S. Role of IL-2 in cancer immunotherapy. Oncoimmunology. 2016;5(6):e1163462.
Stock S, Schmitt M, Sellner L. Optimizing Manufacturing Protocols of Chimeric Antigen Receptor T Cells for Improved Anticancer Immunotherapy. Int J Mol Sci. 2019;20(24):6223.
Teoh PJ, Chng WJ. CAR T-cell therapy in multiple myeloma: more room for improvement. Blood Cancer J. 2021;11(4):84.
Egri N, Ortiz de Landazuri I, San Bartolomé C, Ortega JR, Español-Rego M, Juan M. CART manufacturing process and reasons for academy-pharma collaboration. Immunol Lett. 2020;217:39-48.
Wang X, Rivière I. Clinical manufacturing of CAR T cells: foundation of a promising therapy. Mol Ther Oncolytics. 2016;3:16015.
Vormittag P, Gunn R, Ghorashian S, Veraitch FS. A guide to manufacturing CAR T cell therapies. 2018;53:164-181.
Zhao L, Cao YJ. Engineered T Cell Therapy for Cancer in the Clinic. Front Immunol. 2019;10:2250.
Zhang C, Liu J, Zhong JF, Zhang X. Engineering CAR-T cells. Biomark Res. 2017;5:22.
Poorebrahim M, Sadeghi S, Fakhr E, Abazari MF, Poortahmasebi V, Kheirollahi A, et al. Production of CAR T-cells by GMP-grade lentiviral vectors: latest advances and future prospects. Crit Rev Clin Lab Sci. 2019;56(6):393-419.
Milone MC, O'Doherty U. Clinical use of lentiviral vectors. Leukemia. 2018 ;32(7):1529-1541.
Monjezi R, Miskey C, Gogishvili T, Schleef M, Schmeer M, Einsele H,, et al Enhanced CAR T-cell engineering using non-viral Sleeping Beauty transposition from minicircle vectors. Leukemia. 2017;31(1):186-194.
Kumar P, Nagarajan A, Uchil PD. Electroporation. Cold Spring Harb Protoc. 2019;2019(7).
Hartmann J, Schüßler-Lenz M, Bondanza A, Buchholz CJ. Clinical development of CAR T cells-challenges and opportunities in translating innovative treatment concepts. EMBO Mol Med. 2017;9(9):1183-1197.
Brentjens RJ, Davila ML, Riviere I, et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med. 2013;5(177):177ra38.
Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013;368(16):1509-1518.
Zuo YX, Jia YP, Wu J, Wang JB, Lu AD, Dong LJ, et al. [Chimeric antigen receptors T cells for treatment of 48 relapsed or refractory acute lymphoblastic leukemia children: long term follow up outcomes]. Zhonghua Xue Ye Xue Za Zhi. 2019;40(4):270-275.
Hu GH, Cheng YF, Zuo YX, Chang YJ, Suo P, Wu J, et al. Chimeric Antigens Receptor T Cell Therapy Improve the Prognosis of Pediatric Acute Lymphoblastic Leukemia With Persistent/ Recurrent Minimal Residual Disease in First Complete Remission. Front Immunol. 2022;12:731435.
Spiegel JY, Patel S, Muffly L, Hossain NM, Oak J, Baird JH, et al. CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nat Med. 2021;27(8):1419-1431.
Ma F, Ho JY, Du H, Xuan F, Wu X, Wang Q, et al. Evidence of long-lasting anti-CD19 activity of engrafted CD19 chimeric antigen receptor-modified T cells in a phase I study targeting pediatrics with acute lymphoblastic leukemia. Hematol Oncol. 2019;37(5):601-608.
Fry TJ, Shah NN, Orentas RJ, Stetler Stevenson M, Yuan CM, Ramakrishna S, et al. CD22- targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med. 2018;24(1):20-28.
Shah NN, Lee DW, Yates B, Yuan CM, Shalabi H, Martin S, et al. Long-Term Follow-Up of CD19-CAR T-Cell Therapy in Children and Young Adults With B-ALL. J Clin Oncol. 2021;39(15):1650-1659.
Magnani CF, Gaipa G, Lussana F, Belotti D, Gritti G, Napolitano S, et al. Sleeping Beauty engineered CAR T cells achieve antileukemic activity without severe toxicities. J Clin Invest. 2020;130(11):6021-6033.
Hu GH, Cheng YF, Zuo YX, Chang YJ, Suo P, Wu J, et al. Chimeric Antigens Receptor T Cell Therapy Improve the Prognosis of Pediatric Acute Lymphoblastic Leukemia With Persistent/ Recurrent Minimal Residual Disease in First Complete Remission. Front Immunol. 2022;12:731435.
Cohen AD. CAR T Cells and Other Cellular Therapies for Multiple Myeloma: 2018 Update. American Society of Clinical Oncology Educational Book. Vol 38. Alexandria; :2018.
Rivers J, Annesley C, Summers C, Finney O, Pulsipher MA, Wayne AS, et al. Early Response Data for Pediatric Patients with Non-Hodgkin Lymphoma Treated with CD19 Chimeric Antigen Receptor (CAR) T-Cells. Blood. 2018;132(1):2957.
Dominguez MA, Rodas AC. Enfermedad injerto contra huésped. Rev Cent Dermatol Pascua. 2012;21(3):104-108.
Wegner A, Pacheco S, Céspedes P, Guevara R, Mallea L, Darras E, et al. Enfermedad injerto contra huésped asociada a transfusión. Rev. chil. pediatr. 2007;78(5):500-510.
Santomasso B, Bachier C, Westin J, Rezvani K, Shpall EJ. The Other Side of CAR T-Cell Therapy: Cytokine Release Syndrome, Neurologic Toxicity, and Financial Burden. American Society of Clinical Oncology Educational Book. Vol 39. Alexandria; 2019.
Aplasia Medular [Internet]. Madrid: Grupo Español de Trasplante Hematopoyético y Terapia Celular; 2023. Hemopatías. Disponible en: https:// www.geth.es/pacientes/hemopatias/aplasia-medular
Picanço V, Swiech K, Ribeiro KC, Covas DT. CAR-T Cells for Cancer Treatment: Current Design and Next Frontiers. Methods mol. biol. 2020;2086:1-10.
Delgado MD, Cestari JJ, Lestón AH, Alemano G. Síndrome de lisis tumoral. Revisión bibliográfica a 90 años de su descripción. Rev Nefrol Dial Traspl. 2018;38(2):148-159.
Pérez B, Corral J, Casas AM. Neurotoxicidad por quimioterapia. En: Camps C, Carulla J, Casas AM, González M, Valentín V. Uso de los Fármacos Antiepilépticos en Oncología. Madrid: Dispublic, S. L.;2006.p.109-126
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