The Role of Chimeric Antigen Receptor T-Cell Therapy in Immune-Mediated Neurological Diseases.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
17 Jul 2024
17 Jul 2024
Historique:
revised:
20
05
2024
received:
11
01
2024
accepted:
23
06
2024
medline:
17
7
2024
pubmed:
17
7
2024
entrez:
17
7
2024
Statut:
aheadofprint
Résumé
Despite the use of 'high efficacy' disease-modifying therapies, disease activity and clinical progression of different immune-mediated neurological diseases continue for some patients, resulting in accumulating disability, deteriorating social and mental health, and high economic cost to patients and society. Although autologous hematopoietic stem cell transplant is an effective treatment modality, it is an intensive chemotherapy-based therapy with a range of short- and long-term side-effects. Chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized the treatment of B-cell and other hematological malignancies, conferring long-term remission for otherwise refractory diseases. However, the toxicity of this treatment, particularly cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, and the complexity of production necessitate the need for a high level of specialization at treating centers. Early-phase trials of CAR-T therapies in immune-mediated B cell driven conditions, such as systemic lupus erythematosus, neuromyelitis optica spectrum disorder and myasthenia gravis, have shown dramatic clinical response with few adverse events. Based on the common physiopathology, CAR-T therapy in other immune-mediated neurological disease, including multiple sclerosis, chronic inflammatory polyradiculopathy, autoimmune encephalitis, and stiff person syndrome, might be an effective option for patients, avoiding the need for long-term immunosuppressant medications. It may prove to be a more selective immunoablative approach than autologous hematopoietic stem cell transplant, with potentially increased efficacy and lower adverse events. In this review, we present the state of the art and future directions of the use of CAR-T in such conditions. ANN NEUROL 2024.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
Bhagavati S. Autoimmune disorders of the nervous system: pathophysiology, clinical features, and therapy. Front Neurol 2021;12. https://doi.org/10.3389/fneur.2021.664664.
Sabatino JJ, Pröbstel A‐K, Zamvil SS. B cells in autoimmune and neurodegenerative central nervous system diseases. Nat Rev Neurosci 2019;20:728–745. https://doi.org/10.1038/s41583-019-0233-2.
Cohen JA, Coles AJ, Arnold DL, et al. Alemtuzumab versus interferon beta 1a as first‐line treatment for patients with relapsing‐remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet 2012;380:1819–1828. https://doi.org/10.1016/s0140-6736(12)61769-3.
Hauser SL, Bar‐Or A, Comi G, et al. Ocrelizumab versus interferon Beta‐1a in relapsing multiple sclerosis. N Engl J Med 2017;376:221–234. https://doi.org/10.1056/NEJMoa1601277.
Hauser SL, Bar‐Or A, Cohen JA, et al. Ofatumumab versus Teriflunomide in Multiple Sclerosis. N Engl J Med 2020;383:546–557. https://doi.org/10.1056/NEJMoa1917246.
Polman CH, O'Connor PW, Havrdova E, et al. Placebo‐controlled trial of Natalizumab for relapsing multiple sclerosis. N Engl J Med 2006;354:899–910. https://doi.org/10.1056/NEJMoa044397.
Tahara M, Oeda T, Okada K, et al. Safety and efficacy of rituximab in neuromyelitis optica spectrum disorders (RIN‐1 study): a multicentre, randomised, double‐blind, placebo‐controlled trial. Lancet Neurol 2020;19:298–306. https://doi.org/10.1016/S1474-4422(20)30066-1.
Yamamura T, Kleiter I, Fujihara K, et al. Trial of Satralizumab in Neuromyelitis Optica Spectrum disorder. N Engl J Med 2019;381:2114–2124. https://doi.org/10.1056/NEJMoa1901747.
Cree BAC, Bennett JL, Kim HJ, et al. Inebilizumab for the treatment of neuromyelitis optica spectrum disorder (N‐MOmentum): a double‐blind, randomised placebo‐controlled phase 2/3 trial. Lancet 2019;394:1352–1363. https://doi.org/10.1016/S0140-6736(19)31817-3.
Pittock SJ, Berthele A, Fujihara K, et al. Eculizumab in Aquaporin‐4–positive Neuromyelitis Optica Spectrum disorder. N Engl J Med 2019;381:614–625. https://doi.org/10.1056/NEJMoa1900866.
Montalban PX. Update of the ECTRIMS/EAN guidelines on the treatment of multiple sclerosis. ECTRIMS, 2021.
Sefia E, Pryce G, Meier U‐C, et al. Depletion of CD20 B cells fails to inhibit relapsing mouse experimental autoimmune encephalomyelitis. Mult Scler Relat Disord 2017;14:46–50. https://doi.org/10.1016/j.msard.2017.03.013.
Alexander T, Greco R. Hematopoietic stem cell transplantation and cellular therapies for autoimmune diseases: overview and future considerations from the autoimmune diseases working party (ADWP) of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant 2022;57:1055–1062. https://doi.org/10.1038/s41409-022-01702-w.
Sharrack B et al. Autologous haematopoietic stem cell transplantation and other cellular therapy in multiple sclerosis and immune‐mediated neurological diseases: updated guidelines and recommendations from the EBMT autoimmune diseases working party (ADWP) and the joint accreditation committee of EBMT and ISCT (JACIE). Bone Marrow Transplant 2020;55:283–306. https://doi.org/10.1038/s41409-019-0684-0.
Brittain G et al. Autologous haematopoietic stem cell transplantation for immune‐mediated neurological diseases: what, how, who and why? Pract Neurol 2022;23:139–145. https://doi.org/10.1136/pn-2022-003531.
Burt RK, Balabanov R, Burman J, et al. Effect of Nonmyeloablative hematopoietic stem cell transplantation vs continued disease‐modifying therapy on disease progression in patients with relapsing‐remitting multiple sclerosis: a Randomized clinical trial. JAMA 2019;321:165–174. https://doi.org/10.1001/jama.2018.18743.
Burt RK, Han X, Quigley K, et al. Real‐world application of autologous hematopoietic stem cell transplantation in 507 patients with multiple sclerosis. J Neurol 2022;269:2513–2526. https://doi.org/10.1007/s00415-021-10820-2.
Silfverberg T, Zjukovskaja C, Ljungman P, et al. Haematopoietic stem cell transplantation for treatment of relapsing‐remitting multiple sclerosis in Sweden: an observational cohort study. J Neurol Neurosurg Psychiatry 2024;95:125–133. https://doi.org/10.1136/jnnp-2023-331864.
Muraro PA, Martin R, Mancardi GL, et al. Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis. Nat Rev Neurol 2017;13:391–405. https://doi.org/10.1038/nrneurol.2017.81.
Snowden JA, Badoglio M, Labopin M, et al. Evolution, trends, outcomes, and economics of hematopoietic stem cell transplantation in severe autoimmune diseases. Blood Adv 2017;1:2742–2755. https://doi.org/10.1182/bloodadvances.2017010041.
June CH, Sadelain M. Chimeric antigen receptor therapy. N Engl J Med 2018;379:64–73. https://doi.org/10.1056/NEJMra1706169.
Milone MC, Xu J, Chen SJ, et al. Engineering‐enhanced CAR T cells for improved cancer therapy. Nat Cancer 2021;2:780–793. https://doi.org/10.1038/s43018-021-00241-5.
Kalos M et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med 2011;3:95ra73. https://doi.org/10.1126/scitranslmed.3002842.
Sadelain M, Riviere I, Riddell S. Therapeutic T cell engineering. Nature 2017;545:423–431. https://doi.org/10.1038/nature22395.
European Medicines Agency. Medicines, https://www.ema.europa.eu/en/medicines 2023.
U.S. Food & Drug Administration. Approved cellular and gene therapy products, https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products 2022.
Medicines and Healthcare products Regulatory Agency. Orphan registered medicinal products, https://www.gov.uk/government/publications/orphan-registered-medicinal-products 2023.
Lickefett B, Chu L, Ortiz‐Maldonado V, et al. Lymphodepletion ‐ an essential but undervalued part of the chimeric antigen receptor T‐cell therapy cycle. Front Immunol 2023;14:1303935. https://doi.org/10.3389/fimmu.2023.1303935.
Martínez Bedoya D, Dutoit V, Migliorini D, Allogeneic CART. Cells: an alternative to overcome challenges of CAR T cell therapy in glioblastoma. Front Immunol 2021;12:640082. https://doi.org/10.3389/fimmu.2021.640082.
Depil S, Duchateau P, Grupp SA, et al. 'Off‐the‐shelf' allogeneic CAR T cells: development and challenges. Nat Rev Drug Discovery 2020;19:185–199. https://doi.org/10.1038/s41573-019-0051-2.
Wang D, Quan Y, Yan Q, et al. Targeted disruption of the β2‐microglobulin gene minimizes the immunogenicity of human embryonic stem cells. Stem Cells Transl Med 2015;4:1234–1245. https://doi.org/10.5966/sctm.2015-0049.
Ren J, Liu X, Fang C, et al. Multiplex genome editing to generate universal CAR T cells resistant to PD1 inhibition. Clin Cancer Res 2017;23:2255–2266. https://doi.org/10.1158/1078-0432.Ccr-16-1300.
Zhang L, Meng Y, Feng X, Han Z. CAR‐NK cells for cancer immunotherapy: from bench to bedside. Biomarker Res 2022;10:12. https://doi.org/10.1186/s40364-022-00364-6.
Granit V, Benatar M, Kurtoglu M, et al. Safety and clinical activity of autologous RNA chimeric antigen receptor T‐cell therapy in myasthenia gravis (MG‐001): a prospective, multicentre, open‐label, non‐randomised phase 1b/2a study. Lancet Neurol 2023;22:578–590. https://doi.org/10.1016/S1474-4422(23)00194-1.
Xie B, Li Z, Zhou J, Wang W. Current status and perspectives of dual‐targeting chimeric antigen receptor T‐cell therapy for the treatment of hematological malignancies. Cancers 2022;14:3230. https://doi.org/10.3390/cancers14133230.
Ruffo E, Butchy AA, Tivon Y, et al. Post‐translational covalent assembly of CAR and synNotch receptors for programmable antigen targeting. Nat Commun 2023;14:2463. https://doi.org/10.1038/s41467-023-37863-5.
Doglio M, Alexander T, Del Papa N, et al. New insights in systemic lupus erythematosus: from regulatory T cells to CAR‐T‐cell strategies. J Allergy Clin Immunol 2022;150:1289–1301. https://doi.org/10.1016/j.jaci.2022.08.003.
Doglio M, Ugolini A, Bercher‐Brayer C, et al. Regulatory T cells expressing CD19‐targeted chimeric antigen receptor restore homeostasis in systemic lupus erythematosus. Nat Commun 2024;15:2542. https://doi.org/10.1038/s41467-024-46448-9.
Shimabukuro‐Vornhagen A, Gödel P, Subklewe M, et al. Cytokine release syndrome. J Immunother Cancer 2018;6:56. https://doi.org/10.1186/s40425-018-0343-9.
Garcia Borrega J, Gödel P, Rüger MA, et al. In the eye of the storm: immune‐mediated toxicities associated with CAR‐T cell therapy. Hema 2019;3:e191. https://doi.org/10.1097/hs9.0000000000000191.
Neelapu SS, Tummala S, Kebriaei P, et al. Chimeric antigen receptor T‐cell therapy — assessment and management of toxicities. Nat Rev Clin Oncol 2018;15:47–62. https://doi.org/10.1038/nrclinonc.2017.148.
Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene Ciloleucel CAR T‐cell therapy in refractory large B‐cell lymphoma. N Engl J Med 2017;377:2531–2544. https://doi.org/10.1056/NEJMoa1707447.
Schuster SJ, Bishop MR, Tam CS, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B‐cell lymphoma. N Engl J Med 2019;380:45–56. https://doi.org/10.1056/NEJMoa1804980.
Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B‐cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet 2020;396:839–852. https://doi.org/10.1016/s0140-6736(20)31366-0.
Hayden PJ, Roddie C, Bader P, et al. Management of adults and children receiving CAR T‐cell therapy: 2021 best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the joint accreditation committee of ISCT and EBMT (JACIE) and the European Haematology association (EHA). Ann Oncol 2022;33:259–275. https://doi.org/10.1016/j.annonc.2021.12.003.
Yáñez L, Alarcón A, Sánchez‐Escamilla M, Perales MA. How I treat adverse effects of CAR‐T cell therapy. ESMO Open 2020;4:e000746. https://doi.org/10.1136/esmoopen-2020-000746.
Gazeau N, Liang EC, Wu Q“V”, et al. Anakinra for refractory cytokine release syndrome or immune effector cell‐associated neurotoxicity syndrome after chimeric antigen receptor T cell therapy. Transplant Cell Ther 2023;29:430–437. https://doi.org/10.1016/j.jtct.2023.04.001.
Lakomy T, Akhoundova D, Nilius H, et al. Early use of corticosteroids following CAR T‐cell therapy correlates with reduced risk of high‐grade CRS without negative impact on neurotoxicity or treatment outcome. Biomolecules 2023;13:382.
Tallantyre EC, Evans NA, Parry‐Jones J, et al. Neurological updates: neurological complications of CAR‐T therapy. J Neurol 2021;268:1544–1554. https://doi.org/10.1007/s00415-020-10237-3.
Mahdi J, Dietrich J, Straathof K, et al. Tumor inflammation‐associated neurotoxicity. Nat Med 2023;29:803–810. https://doi.org/10.1038/s41591-023-02276-w.
Gatto L et al. CAR‐T cells neurotoxicity from consolidated practice in hematological malignancies to fledgling experience in CNS tumors: fill the gap. Front Oncol 2023;13. https://doi.org/10.3389/fonc.2023.1206983.
Berdeja JG, Madduri D, Usmani SZ, et al. Ciltacabtagene autoleucel, a B‐cell maturation antigen‐directed chimeric antigen receptor T‐cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE‐1): a phase 1b/2 open‐label study. Lancet 2021;398:314–324. https://doi.org/10.1016/S0140-6736(21)00933-8.
Mohyuddin GR, Banerjee R, Alam Z, et al. Rethinking mechanisms of neurotoxicity with BCMA directed therapy. Crit Rev Oncol Hematol 2021;166:103453. https://doi.org/10.1016/j.critrevonc.2021.103453.
Osório C, Chacón PJ, White M, et al. Selective regulation of axonal growth from developing hippocampal neurons by tumor necrosis factor superfamily member APRIL. Mol Cell Neurosci 2014;59:24–36. https://doi.org/10.1016/j.mcn.2014.01.002.
Qin C, Tian DS, Zhou LQ, et al. Anti‐BCMA CAR T‐cell therapy CT103A in relapsed or refractory AQP4‐IgG seropositive neuromyelitis optica spectrum disorders: phase 1 trial interim results. Signal Transduct Target Ther 2023;8:5. https://doi.org/10.1038/s41392-022-01278-3.
Hines MR et al. Immune effector cell‐associated Hemophagocytic Lymphohistiocytosis‐like syndrome. Transpl Cell Ther 2023;29:e431–e438. https://doi.org/10.1016/j.jtct.2023.03.006.
Rejeski K et al. Immune effector cell‐associated Hematotoxicity (ICAHT): EHA/EBMT consensus grading and best practice recommendations. Blood J 2023;142:865–877. https://doi.org/10.1182/blood.2023020578.
Lichtenstein DA, Schischlik F, Shao L, et al. Characterization of HLH‐like manifestations as a CRS variant in patients receiving CD22 CAR T cells. Blood 2021;138:2469–2484. https://doi.org/10.1182/blood.2021011898.
Levine BL, Pasquini MC, Connolly JE, et al. Unanswered questions following reports of secondary malignancies after CAR‐T cell therapy. Nat Med 2024;30:338–341. https://doi.org/10.1038/s41591-023-02767-w.
Elsallab M, Ellithi M, Lunning MA, et al. Second primary malignancies after commercial CAR T cell therapy: analysis of FDA adverse events reporting system (FAERS). Blood 2024;143:2099–2105. https://doi.org/10.1182/blood.2024024166.
Verdun N, Marks P. Secondary cancers after chimeric antigen receptor T‐cell therapy. N Engl J Med 2024;390:584–586. https://doi.org/10.1056/NEJMp2400209.
Harrison SJ, Nguyen T, Rahman M, et al. CAR+ T‐cell lymphoma post Ciltacabtagene Autoleucel therapy for relapsed refractory multiple myeloma. Blood 2023;142:6939. https://doi.org/10.1182/blood-2023-178806.
Mackensen A, Müller F, Mougiakakos D, et al. Anti‐CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med 2022;28:2124–2132. https://doi.org/10.1038/s41591-022-02017-5.
Nunez D et al. Cytokine and reactivity profiles in SLE patients following anti‐CD19 CART therapy. Mol Ther‐Methods Clin Dev 2023;31. https://doi.org/10.1016/j.omtm.2023.08.023.
Müller F, Taubmann J, Bucci L, et al. CD19 CAR T‐cell therapy in autoimmune disease—a case series with follow‐up. N Engl J Med 2024;390:687–700. https://doi.org/10.1056/NEJMoa2308917.
Müller F, Boeltz S, Knitza J, et al. CD19‐targeted CAR T cells in refractory antisynthetase syndrome. Lancet 2023;401:815–818. https://doi.org/10.1016/S0140-6736(23)00023-5.
Bergmann C, Müller F, Distler JHW, et al. Treatment of a patient with severe systemic sclerosis (SSc) using CD19‐targeted CAR T cells. Ann Rheum Dis 2023;82:1117–1120. https://doi.org/10.1136/ard-2023-223952.
Baker D, Jacobs BM, Gnanapavan S, et al. Plasma cell and B cell‐targeted treatments for use in advanced multiple sclerosis. Mult Scler Relat Disord 2019;35:19–25. https://doi.org/10.1016/j.msard.2019.06.030.
Giovannoni G, Hawkes CH, Lechner‐Scott J, et al. Are we ready for CD19‐targeted CAR T‐cell therapies in MS? Mult Scler Relat Disord 2023;70:104590. https://doi.org/10.1016/j.msard.2023.104590.
Giovannoni G, Hawkes CH, Lechner‐Scott J, et al. Is EBV the cause of multiple sclerosis? Mult Scler Relat Disord 2022;58:103636. https://doi.org/10.1016/j.msard.2022.103636.
Nair R, Ayers A, Nastoupil LJ, et al. CD19 CAR‐T outcomes in patients with EBV‐positive DLBCL. Blood 2022;140:3800–3802. https://doi.org/10.1182/blood-2022-171120.
Smith C, Khanna R. Adoptive T‐cell therapy targeting Epstein‐Barr virus as a treatment for multiple sclerosis. Clin Transl Immunol 2023;12:e1444. https://doi.org/10.1002/cti2.1444.
De Paula Pohl A, Schmidt A, Zhang A‐H, et al. Engineered regulatory T cells expressing myelin‐specific chimeric antigen receptors suppress EAE progression. Cell Immunol 2020;358:104222. https://doi.org/10.1016/j.cellimm.2020.104222.
Fransson M, Piras E, Burman J, et al. CAR/FoxP3‐engineered T regulatory cells target the CNS and suppress EAE upon intranasal delivery. J Neuroinflammation 2012;9:112. https://doi.org/10.1186/1742-2094-9-112.
Oh S, Mao X, Manfredo‐Vieira S, et al. Precision targeting of autoantigen‐specific B cells in muscle‐specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells. Nat Biotechnol 2023;41:1229–1238. https://doi.org/10.1038/s41587-022-01637-z.
Reincke SM et al. Chimeric autoantibody receptor T cells deplete NMDA receptor‐specific B cells. Cell 2023;186:5084–5097. https://doi.org/10.1016/j.cell.2023.10.001.
Gupta S et al. CAR‐T cell–mediated B‐cell depletion in central nervous system autoimmunity. Neurology 2023;10:e200080. https://doi.org/10.1212/NXI.0000000000200080.
Haghikia A et al. Anti‐CD19 CAR T cells for refractory myasthenia gravis. Lancet Neurol 2023;22:1104–1105. https://doi.org/10.1016/S1474-4422(23)00375-7.
Fischbach F, Richter J, Pfeffer LK, et al. CD19‐targeted chimeric antigen receptor T cell therapy in two patients with multiple sclerosis. Med 2024;5:550–558.e2. https://doi.org/10.1016/j.medj.2024.03.002.
Mullard A. CAR‐T therapy for multiple sclerosis enters US trials for first time. Nature 2024. https://doi.org/10.1038/d41586-024-00470-5.
Greco R, Alexander T, delPapa N, et al. Innovative cellular therapies for autoimmune diseases: expert‐based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee. EClinicalMedicine 2024;69:102476. https://doi.org/10.1016/j.eclinm.2024.102476.