Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of B-cell malignancies and has attracted growing interest for autoimmune and allergic diseases. Because these disorders are often driven by pathogenic B cells that produce autoantibodies or allergen-specific IgE, they represent promising targets for CAR-T–based therapies. Studies have demonstrated that CD19-targeted CAR-T cells can induce deep and sustained drug-free remissions in severe autoimmune diseases, including systemic lupus erythematosus, idiopathic inflammatory myositis, and systemic sclerosis. Early evidence from multiple independent centers now extending to 36 months of follow-up indicates that CAR-T therapy may enable long-term disease control and potentially curative outcomes in carefully selected patients, rather than merely alleviating symptoms. Concurrently, preclinical research is advancing CAR-T approaches for allergic diseases, with efforts focused on eliminating IgE-producing B cells and engineering regulatory CAR-T cells to restore immune tolerance. In this review, we synthesized the mechanisms underlying CAR-T function, along with emerging preclinical data and clinical outcomes supporting its use in immune-mediated disorders. We also explored innovative strategies, including chimeric autoantibody receptor (CAAR) T cells, dual-targeting constructs, and next-generation CAR designs incorporating safety switches to improve efficacy and minimize toxicity. Despite promising early results, several challenges remain, including limited long-term safety data, the need for standardized patient selection criteria, manufacturing complexity, and questions regarding optimal timing and disease stage for intervention. Continued advances in cell engineering and scalable production are expected to address these limitations. Overall, CAR-T therapy represents a promising and potentially transformative approach for treating refractory autoimmune and allergic diseases.
Citation: Cromwel Tepap Zemnou, Ramelle Ngakam. Chimeric antigen receptor T cells in autoimmune diseases and allergy: From bench to bedside[J]. AIMS Allergy and Immunology, 2026, 10(3): 143-183. doi: 10.3934/Allergy.2026012
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of B-cell malignancies and has attracted growing interest for autoimmune and allergic diseases. Because these disorders are often driven by pathogenic B cells that produce autoantibodies or allergen-specific IgE, they represent promising targets for CAR-T–based therapies. Studies have demonstrated that CD19-targeted CAR-T cells can induce deep and sustained drug-free remissions in severe autoimmune diseases, including systemic lupus erythematosus, idiopathic inflammatory myositis, and systemic sclerosis. Early evidence from multiple independent centers now extending to 36 months of follow-up indicates that CAR-T therapy may enable long-term disease control and potentially curative outcomes in carefully selected patients, rather than merely alleviating symptoms. Concurrently, preclinical research is advancing CAR-T approaches for allergic diseases, with efforts focused on eliminating IgE-producing B cells and engineering regulatory CAR-T cells to restore immune tolerance. In this review, we synthesized the mechanisms underlying CAR-T function, along with emerging preclinical data and clinical outcomes supporting its use in immune-mediated disorders. We also explored innovative strategies, including chimeric autoantibody receptor (CAAR) T cells, dual-targeting constructs, and next-generation CAR designs incorporating safety switches to improve efficacy and minimize toxicity. Despite promising early results, several challenges remain, including limited long-term safety data, the need for standardized patient selection criteria, manufacturing complexity, and questions regarding optimal timing and disease stage for intervention. Continued advances in cell engineering and scalable production are expected to address these limitations. Overall, CAR-T therapy represents a promising and potentially transformative approach for treating refractory autoimmune and allergic diseases.
| [1] | GBD 2019 Diseases and Injuries Collaborators.Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet (2020) 396: 1204-1222. https://doi.org/10.1016/S0140-6736(20)30925-9 |
| [2] |
Pisetsky DS, Lipsky PE (2020) New insights into the role of antinuclear antibodies in systemic lupus erythematosus. Nat Rev Rheumatol 16: 565-579. https://doi.org/10.1038/s41584-020-0480-7 
|
| [3] |
Rosenblum MD, Remedios KA, Abbas AK (2015) Mechanisms of human autoimmunity. J Clin Invest 125: 2228-2233. https://doi.org/10.1172/JCI78088
|
| [4] |
Dharmage SC, Perret JL, Custovic A (2019) Epidemiology of asthma in children and adults. Front Pediatr 7: 246. https://doi.org/10.3389/fped.2019.00246
|
| [5] |
Loh W, Tang MLK (2018) The epidemiology of food allergy in the global context. Int J Environ Res Public Health 15: 2043. https://doi.org/10.3390/ijerph15092043
|
| [6] |
Shamji MH, Valenta R, Jardetzky T, et al. (2021) The role of allergen-specific IgE, IgG and IgA in allergic disease. Allergy 76: 3627-3641. https://doi.org/10.1111/all.14908
|
| [7] |
Meffre E, O'Connor KC (2019) Impaired B-cell tolerance checkpoints promote the development of autoimmune diseases and pathogenic autoantibodies. Immunol Rev 292: 90-101. https://doi.org/10.1111/imr.12821
|
| [8] |
Arbuckle MR, McClain MT, Rubertone MV, et al. (2003) Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 349: 1526-1533. https://doi.org/10.1056/NEJMoa021933
|
| [9] |
Gould HJ, Sutton BJ (2008) IgE in allergy and asthma today. Nat Rev Immunol 8: 205-217. https://doi.org/10.1038/nri2273
|
| [10] |
Jiménez-Saiz R, Chu DK, Mandur TS, et al. (2017) Lifelong memory responses perpetuate humoral TH2 immunity and anaphylaxis in food allergy. J Allergy Clin Immunol 140: 1604-1615. https://doi.org/10.1016/j.jaci.2017.01.018
|
| [11] |
Asrat S, Kaur N, Liu X, et al. (2020) Chronic allergen exposure drives accumulation of long-lived IgE plasma cells in the bone marrow. Sci Immunol 5: eaav8402. https://doi.org/10.1126/sciimmunol.aav8402
|
| [12] |
Md Yusof MY, Vital EM, Buch MH (2020) B cell therapies and targeted therapies in systemic lupus erythematosus. Rheumatology (Oxford) 59: iii67-iii74.
|
| [13] |
Stone JH, Merkel PA, Spiera R, et al. (2010) Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med 363: 221-232. https://doi.org/10.1056/NEJMoa0909905
|
| [14] |
Furie R, Rovin BH, Houssiau F, et al. (2020) Two-year, randomized, controlled trial of belimumab in lupus nephritis. N Engl J Med 383: 1117-1128. https://doi.org/10.1056/NEJMoa2001180
|
| [15] |
Hiepe F, Dörner T, Hauser AE, et al. (2011) Long-lived autoreactive plasma cells drive persistent autoimmune inflammation. Nat Rev Rheumatol 7: 170-178. https://doi.org/10.1038/nrrheum.2011.1
|
| [16] |
Reddy V, Jayne D, Close D, et al. (2013) B-cell depletion in SLE: Clinical and trial experience with rituximab and ocrelizumab and implications for study design. Arthritis Res Ther 15: S2. https://doi.org/10.1186/ar3910
|
| [17] |
Cambridge G, Leandro MJ, Edwards JC, et al. (2003) Serologic changes following B lymphocyte depletion therapy for rheumatoid arthritis. Arthritis Rheum 48: 2146-2154. https://doi.org/10.1002/art.11181
|
| [18] |
June CH, Sadelain M (2018) Chimeric antigen receptor therapy. N Engl J Med 379: 64-73. https://doi.org/10.1056/NEJMra1706169
|
| [19] |
Sterner RC, Sterner RM (2021) CAR-T cell therapy: Current limitations and potential strategies. Blood Cancer J 11: 69. https://doi.org/10.1038/s41408-021-00459-7
|
| [20] |
Maude SL, Laetsch TW, Buechner J, et al. (2018) Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med 378: 439-448. https://doi.org/10.1056/NEJMoa1709866
|
| [21] |
Schuster SJ, Bishop MR, Tam CS, et al. (2019) Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med 380: 45-56. https://doi.org/10.1056/NEJMoa1804980
|
| [22] |
Ellebrecht CT, Bhoj VG, Nace A, et al. (2016) Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease. Science 353: 179-184. https://doi.org/10.1126/science.aaf6756
|
| [23] |
Sadelain M, Brentjens R, Rivière I (2013) The basic principles of chimeric antigen receptor design. Cancer Discov 3: 388-398. https://doi.org/10.1158/2159-8290.CD-12-0548
|
| [24] |
Guedan S, Calderon H, Posey AD, et al. (2019) Engineering and design of chimeric antigen receptors. Mol Ther Methods Clin Dev 12: 145-156. https://doi.org/10.1016/j.omtm.2018.12.009
|
| [25] |
Eshhar Z, Waks T, Gross G, et al. (1993) 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 USA 90: 720-724. https://doi.org/10.1073/pnas.90.2.720
|
| [26] |
Brentjens RJ, Davila ML, Riviere I, et al. (2013) CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med 5: 177ra38. https://doi.org/10.1126/scitranslmed.3005930
|
| [27] |
Chmielewski M, Abken H (2015) TRUCKs: The fourth generation of CARs. Expert Opin Biol Ther 15: 1145-1154. https://doi.org/10.1517/14712598.2015.1046430
|
| [28] |
Alabanza L, Pegues M, Geldres C, et al. (2017) Function of novel anti-CD19 chimeric antigen receptors with human variable regions is affected by hinge and transmembrane domains. Mol Ther 25: 2452-2465. https://doi.org/10.1016/j.ymthe.2017.07.013
|
| [29] |
Kawalekar OU, O'Connor RS, Fraietta JA, et al. (2016) Distinct signaling of coreceptors regulates specific metabolism pathways and impacts memory development in CAR T cells. Immunity 44: 380-390. https://doi.org/10.1016/j.immuni.2016.01.021
|
| [30] | Shah NN, Fry TJ (2019) Mechanisms of resistance to CAR T cell therapy. Nat Rev Clin Oncol 16: 372-385. https://doi.org/10.1038/s41571-019-0184-6 |
| [31] |
Wang X, Rivière I (2016) Clinical manufacturing of CAR T cells: Foundation of a promising therapy. Mol Ther Oncolytics 3: 16015. https://doi.org/10.1038/mto.2016.15
|
| [32] |
Levine BL, Miskin J, Wonnacott K, et al. (2017) Global manufacturing of CAR T cell therapy. Mol Ther Methods Clin Dev 4: 92-101. https://doi.org/10.1016/j.omtm.2016.12.006
|
| [33] |
Fraietta JA, Lacey SF, Orlando EJ, et al. (2018) Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia. Nat Med 24: 563-571. https://doi.org/10.1038/s41591-018-0010-1
|
| [34] |
Hartmann J, Schüßler-Lenz M, Bondanza A, et al. (2017) Clinical development of CAR T cells—challenges and opportunities in translating innovative treatment concepts. EMBO Mol Med 9: 1183-1197. https://doi.org/10.15252/emmm.201607485
|
| [35] |
Benjamin R, Graham C, Yallop D, et al. (2020) Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia: Results of two phase 1 studies. Lancet 396: 1885-1894. https://doi.org/10.1016/S0140-6736(20)32334-5
|
| [36] |
Depil S, Duchateau P, Grupp SA, et al. (2020) ‘Off-the-shelf’ allogeneic CAR T cells: Development and challenges. Nat Rev Drug Discov 19: 185-199. https://doi.org/10.1038/s41573-019-0051-2
|
| [37] |
Davenport AJ, Cross RS, Watson KA, et al. (2018) Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity. Proc Natl Acad Sci USA 115: E2068-E2076. https://doi.org/10.1073/pnas.1716266115
|
| [38] |
Martinez M, Moon EK (2019) CAR T cells for solid tumors: New strategies for finding, infiltrating, and surviving in the tumor microenvironment. Front Immunol 10: 128. https://doi.org/10.3389/fimmu.2019.00128
|
| [39] |
Hay KA, Hanafi LA, Li D, et al. (2017) Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy. Blood 130: 2295-2306. https://doi.org/10.1182/blood-2017-06-793141
|
| [40] |
Melenhorst JJ, Chen GM, Wang M, et al. (2022) Decade-long leukaemia remissions with persistence of CD4+ CAR T cells. Nature 602: 503-509. https://doi.org/10.1038/s41586-021-04390-6
|
| [41] |
Tsokos GC, Lo MS, Costa Reis P, et al. (2016) New insights into the immunopathogenesis of systemic lupus erythematosus. Nat Rev Rheumatol 12: 716-730. https://doi.org/10.1038/nrrheum.2016.186
|
| [42] |
Mariette X, Criswell LA (2018) Primary Sjögren's syndrome. N Engl J Med 378: 931-939. https://doi.org/10.1056/NEJMcp1702514
|
| [43] |
Allanore Y, Simms R, Distler O, et al. (2015) Systemic sclerosis. Nat Rev Dis Primers 1: 15002. https://doi.org/10.1038/nrdp.2015.2
|
| [44] |
Lundberg IE, Fujimoto M, Vencovsky J, et al. (2021) Idiopathic inflammatory myopathies. Nat Rev Dis Primers 7: 86. https://doi.org/10.1038/s41572-021-00321-x
|
| [45] |
Mougiakakos D, Krönke G, Völkl S, et al. (2021) CD19-targeted CAR T cells in refractory systemic lupus erythematosus. N Engl J Med 385: 567-569. https://doi.org/10.1056/NEJMc2107725
|
| [46] |
Park JH, Rivière I, Gonen M, et al. (2018) Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med 378: 449-459. https://doi.org/10.1056/NEJMoa1709919
|
| [47] | Khurana D, Sharma S (2020) CAR T cells: The transformative therapy and its landscape. Immunotherapy 12: 979-993. |
| [48] |
Wang K, Wei G, Liu D (2012) CD19: A biomarker for B cell development, lymphoma diagnosis and therapy. Exp Hematol Oncol 1: 36. https://doi.org/10.1186/2162-3619-1-36
|
| [49] | Tian DS, Qin C, Dong MH, et al. (2024) B cell lineage reconstitution underlies CAR-T cell therapeutic efficacy in patients with refractory myasthenia gravis. EMBO Mol Med 16: 966-987. https://doi.org/10.1038/s44321-024-00043-z |
| [50] |
Snowden JA, Sharrack B, Akil M, et al. (2018) Autologous haematopoietic stem cell transplantation (aHSCT) for severe resistant autoimmune and inflammatory diseases—a guide for the generalist. Clin Med 18: 329-334. https://doi.org/10.7861/clinmedicine.18-4-329
|
| [51] |
Dörner T, Furie R (2019) Novel paradigms in systemic lupus erythematosus. Lancet 393: 2344-2358. https://doi.org/10.1016/S0140-6736(19)30546-X
|
| [52] |
Müller F, Taubmann J, Bucci L, et al. (2023) CD19-targeted CAR T cells in refractory antisynthetase syndrome. Lancet 401: 815-818. https://doi.org/10.1016/S0140-6736(23)00023-5
|
| [53] |
Bhoj VG, Arhontoulis D, Wertheim G, et al. (2016) Persistence of long-lived plasma cells and humoral immunity in individuals responding to CD19-directed CAR T-cell therapy. Blood 128: 360-370. https://doi.org/10.1182/blood-2016-01-694356
|
| [54] |
Perry DK, Burns JM, Pollinger HS, et al. (2009) Proteasome inhibition causes apoptosis of normal human plasma cells preventing alloantibody production. Am J Transplant 9: 201-209. https://doi.org/10.1111/j.1600-6143.2008.02461.x
|
| [55] |
Kansal R, Richardson N, Neeli I, et al. (2019) Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus. Sci Transl Med 11: eaav1648. https://doi.org/10.1126/scitranslmed.aav1648
|
| [56] |
Jin X, Xu Q, Pu C, et al. (2021) Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus. Cell Mol Immunol 18: 1896-1903. https://doi.org/10.1038/s41423-020-0472-1
|
| [57] |
Schett G, Mackensen A, Mougiakakos D (2023) CAR T-cell therapy in autoimmune diseases. Lancet 402: 2034-2044. https://doi.org/10.1016/S0140-6736(23)01126-1
|
| [58] |
Chung JB, Brudno JN, Kochenderfer JN (2024) Chimeric antigen receptor T cell therapy for autoimmune disease. Nat Rev Immunol 24: 830-845. https://doi.org/10.1038/s41577-024-01035-3
|
| [59] |
Amber KT, Hertl M (2015) An assessment of treatment history and its association with clinical outcomes and relapse in 155 pemphigus patients with response to a single cycle of rituximab. J Eur Acad Dermatol Venereol 29: 777-782. https://doi.org/10.1111/jdv.12678
|
| [60] |
Lee J, Lundgren DK, Mao X, et al. (2020) Antigen-specific B cell depletion for precision therapy of mucosal pemphigus vulgaris. J Clin Invest 130: 6317-6324. https://doi.org/10.1172/JCI138416
|
| [61] |
Oh S, Mao X, Manfredo-Vieira S, et al. (2023) Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells. Nat Biotechnol 41: 1229-1238. https://doi.org/10.1038/s41587-022-01637-z
|
| [62] |
Ellebrecht CT, Payne AS (2017) Setting the target for pemphigus therapy. JCI Insight 2: e92021. https://doi.org/10.1172/jci.insight.92021
|
| [63] |
Hauser SL, Bar-Or A, Comi G, et al. (2017) Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med 376: 221-234. https://doi.org/10.1056/NEJMoa1601277
|
| [64] |
McInnes IB, Schett G (2017) Pathogenetic insights from the treatment of rheumatoid arthritis. Lancet 389: 2328-2337. https://doi.org/10.1016/S0140-6736(17)31472-1
|
| [65] |
Zhang L, Sosinowski T, Cox AR, et al. (2019) Chimeric antigen receptor (CAR) T cells targeting a pathogenic MHC class II:peptide complex modulate the progression of autoimmune diabetes. J Autoimmun 96: 50-58. https://doi.org/10.1016/j.jaut.2018.08.004
|
| [66] |
Mackensen A, Müller F, Mougiakakos D, et al. (2022) Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med 28: 2124-2132. https://doi.org/10.1038/s41591-022-02017-5
|
| [67] |
Franklyn K, Lau CS, Navarra SV, et al. (2016) Definition and initial validation of a Lupus Low Disease Activity State (LLDAS). Ann Rheum Dis 75: 1615-1621. https://doi.org/10.1136/annrheumdis-2015-207726
|
| [68] |
Yang C, Sun C, Tan B, et al. (2025) Allogeneic anti-CD19 CAR-T cells induce remission in refractory systemic lupus erythematosus. Cell Res 35: 607-609. https://doi.org/10.1038/s41422-025-01128-1
|
| [69] |
Hill JA, Seo SK (2020) How I prevent infections in patients receiving CD19-targeted chimeric antigen receptor T cells for B-cell malignancies. Blood 136: 925-935. https://doi.org/10.1182/blood.2019004000
|
| [70] |
Lee DW, Santomasso BD, Locke FL, et al. (2019) ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant 25: 625-638. https://doi.org/10.1016/j.bbmt.2018.12.758
|
| [71] |
Müller F, Taubmann J, Bucci L, et al. (2024) CD19 CAR T-cell therapy in autoimmune disease—a case series with follow-up. N Engl J Med 390: 687-700. https://doi.org/10.1056/NEJMoa2308917
|
| [72] |
Lundberg IE, de Visser M, Werth VP (2018) Classification of myositis. Nat Rev Rheumatol 14: 269-278. https://doi.org/10.1038/nrrheum.2018.41
|
| [73] |
Khanna D, Spino C, Johnson S, et al. (2020) Abatacept in early diffuse cutaneous systemic sclerosis: Results of a phase 2 investigator-initiated, multicenter, double-blind randomized placebo-controlled trial. Arthritis Rheumatol 72: 125-136. https://doi.org/10.1002/art.41055
|
| [74] |
Furer V, Rondaan C, Heijstek MW, et al. (2020) 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis 79: 39-52. https://doi.org/10.1136/annrheumdis-2019-215882
|
| [75] |
Yu Q, Wang D, Li Z, et al. (2025) Long-term safety and efficacy of the fully human CAR-T therapy CT103A in relapsed/refractory multiple myeloma. Mol Ther 33: 2768-2777. https://doi.org/10.1016/j.ymthe.2024.11.013
|
| [76] |
Dao LTM, Vu TT, Nguyen QT, et al. (2024) Current cell therapies for systemic lupus erythematosus. Stem Cells Transl Med 13: 859-872. https://doi.org/10.1093/stcltm/szae044
|
| [77] |
Luo W, Weisel F, Shlomchik MJ (2018) B cell receptor and CD40 signaling are rewired for synergistic induction of the c-Myc transcription factor in germinal center B cells. Immunity 48: 313-326. https://doi.org/10.1016/j.immuni.2018.01.008
|
| [78] | ClinicalTrials.govAnti-CD19 CAR T cells in patients with SLE (Systemic Lupus Erythematosus) (2017). NCT03030976. Available from: https://clinicaltrials.gov/ct2/show/NCT03030976 |
| [79] | Shan L, Wang Z, Li S, et al. (2026) Autologous CD19 CAR-T cell therapy for pediatric and adult systemic lupus erythematosus: A phase 1/2 trial. Mol Ther . https://doi.org/10.1016/j.ymthe.2026.03.037 |
| [80] | ClinicalTrials.govBCMA targeted CAR-T cells therapy for refractory SLE (SLE) (2021). NCT05030779. Available from: https://clinicaltrials.gov/ct2/show/NCT05030779 |
| [81] |
Baker DJ, June CH (2022) CAR T therapy extends its reach to autoimmune diseases. Cell 185: 4471-4473. https://doi.org/10.1016/j.cell.2022.10.026
|
| [82] | ClinicalTrials.govDsg3-CAAR T cells for mucosal dominant pemphigus vulgaris (2026). NCT04422912. Available from: https://clinicaltrials.gov/ct2/show/NCT04422912 |
| [83] |
Fanouriakis A, Kostopoulou M, Alunno A, et al. (2019) 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis 78: 736-745. https://doi.org/10.1136/annrheumdis-2019-215089
|
| [84] |
Sullivan KM, Goldmuntz EA, Keyes-Elstein L, et al. (2018) Myeloablative autologous stem-cell transplantation for severe scleroderma. N Engl J Med 378: 35-47. https://doi.org/10.1056/NEJMoa1703327
|
| [85] |
Alexander T, Greco R, Snowden JA (2021) Hematopoietic stem cell transplantation for autoimmune disease. Annu Rev Med 72: 215-228. https://doi.org/10.1146/annurev-med-070119-115617
|
| [86] |
Dorner T, Radbruch A, Burmester GR (2009) B-cell-directed therapies for autoimmune disease. Nat Rev Rheumatol 5: 433-441. https://doi.org/10.1038/nrrheum.2009.141
|
| [87] | Platts-Mills TAE, Commins SP, Schuyler AJ, et al. (2023) New concepts in the pathogenesis of allergic respiratory disease in 2023. J Allergy Clin Immunol 152: 1045-1055. |
| [88] |
Teach SJ, Gill MA, Togias A, et al. (2015) Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations. J Allergy Clin Immunol 136: 1476-1485. https://doi.org/10.1016/j.jaci.2015.09.008
|
| [89] |
Chang TW, Chen C, Lin CJ, et al. (2015) The potential pharmacologic mechanisms of omalizumab in patients with chronic spontaneous urticaria. J Allergy Clin Immunol 135: 337-342. https://doi.org/10.1016/j.jaci.2014.04.036
|
| [90] |
Miranda-Waldetario MCG, Fernandes-Braga W, Curotto de Lafaille MA (2026) Type 2 IgG Memory B Cells and Long-Lived IgE Plasma Cells in the Persistence of Allergy. Immunol Rev 337: e70089. https://doi.org/10.1111/imr.70089
|
| [91] |
Brightbill HD, Jeet S, Lin Z, et al. (2010) Antibodies specific for a segment of human membrane IgE deplete IgE-producing B cells in humanized mice. J Clin Invest 120: 2218-2229. https://doi.org/10.1172/JCI40141
|
| [92] |
Chen JB, Wu PC, Hung AF, et al. (2010) Unique epitopes on CϵmX in IgE-B cell receptors are potentially applicable for targeting IgE-committed B cells. J Immunol 184: 1748-1756. https://doi.org/10.4049/jimmunol.0902437
|
| [93] |
Hoh RA, Joshi SA, Lee JY, et al. (2020) Origins and clonal convergence of gastrointestinal IgE+ B cells in human peanut allergy. Sci Immunol 5: eaay4209. https://doi.org/10.1126/sciimmunol.aay4209
|
| [94] |
Croote D, Darmanis S, Nadeau KC, et al. (2018) High-affinity allergen-specific human antibodies cloned from single IgE B cell transcriptomes. Science 362: 1306-1309. https://doi.org/10.1126/science.aau2599
|
| [95] |
Togias A, Cooper SF, Acebal ML, et al. (2017) Addendum guidelines for the prevention of peanut allergy in the United States: Report of the national institute of allergy and infectious diseases-sponsored expert panel. J Allergy Clin Immunol 139: 29-44. https://doi.org/10.1016/j.jaci.2016.10.010
|
| [96] |
Raffin C, Vo LT, Bluestone JA (2020) Treg cell-based therapies: Challenges and perspectives. Nat Rev Immunol 20: 158-172. https://doi.org/10.1038/s41577-019-0232-6
|
| [97] |
Palomares O, Akdis M, Martin-Fontecha M, et al. (2017) Mechanisms of immune regulation in allergic diseases: The role of regulatory T and B cells. Immunol Rev 278: 219-236. https://doi.org/10.1111/imr.12555
|
| [98] |
Boardman DA, Philippeos C, Fruhwirth GO, et al. (2017) Expression of a chimeric antigen receptor specific for donor HLA class I enhances the potency of human regulatory T cells in preventing human skin transplant rejection. Am J Transplant 17: 931-943. https://doi.org/10.1111/ajt.14185
|
| [99] |
MacDonald KG, Hoeppli RE, Huang Q, et al. (2016) Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor. J Clin Invest 126: 1413-1424. https://doi.org/10.1172/JCI82771
|
| [100] |
Dawson NAJ, Lamarche C, Hooper RL, et al. (2019) Systematic testing and specificity mapping of alloantigen-specific chimeric antigen receptors in regulatory T cells. JCI Insight 4: e123672. https://doi.org/10.1172/jci.insight.123672
|
| [101] |
Romano M, Fanelli G, Albany CJ, et al. (2019) Past, present, and future of regulatory T cell therapy in transplantation and autoimmunity. Front Immunol 10: 43. https://doi.org/10.3389/fimmu.2019.00043
|
| [102] |
Cox L, Platts-Mills TAE, Finegold I, et al. (2007) American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force Report on omalizumab-associated anaphylaxis. J Allergy Clin Immunol 120: 1373-1377. https://doi.org/10.1016/j.jaci.2007.09.032
|
| [103] |
Mpairwe H, Amoah AS (2019) Parasites and allergy: Observations from Africa. Parasite Immunol 41: e12589. https://doi.org/10.1111/pim.12589
|
| [104] |
Santos AF, James LK, Bahnson HT, et al. (2015) IgG4 inhibits peanut-induced basophil and mast cell activation in peanut-tolerant children sensitized to peanut major allergens. J Allergy Clin Immunol 135: 1249-1256. https://doi.org/10.1016/j.jaci.2015.01.012
|
| [105] |
Ohkura N, Yasumizu Y, Kitagawa Y, et al. (2020) Regulatory T cell-specific epigenomic region variants are a key determinant of susceptibility to common autoimmune diseases. Immunity 52: 1119-1132. https://doi.org/10.1016/j.immuni.2020.04.006
|
| [106] |
Shimabukuro-Vornhagen A, Gödel P, Subklewe M, et al. (2018) Cytokine release syndrome. J Immunother Cancer 6: 56. https://doi.org/10.1186/s40425-018-0343-9
|
| [107] |
Fajgenbaum DC, June CH (2020) Cytokine storm. N Engl J Med 383: 2255-2273. https://doi.org/10.1056/NEJMra2026131
|
| [108] |
Schubert ML, Schmitt M, Wang L, et al. (2021) Side-effect management of chimeric antigen receptor (CAR) T-cell therapy. Ann Oncol 32: 34-48. https://doi.org/10.1016/j.annonc.2020.10.478
|
| [109] |
Neelapu SS, Tummala S, Kebriaei P, et al. (2018) Chimeric antigen receptor T-cell therapy—assessment and management of toxicities. Nat Rev Clin Oncol 15: 47-62. https://doi.org/10.1038/nrclinonc.2017.148
|
| [110] |
Le RQ, Li L, Yuan W, et al. (2018) FDA approval summary: Tocilizumab for treatment of chimeric antigen receptor T cell-induced severe or life-threatening cytokine release syndrome. Oncologist 23: 943-947. https://doi.org/10.1634/theoncologist.2018-0028
|
| [111] |
Strati P, Ahmed S, Kebriaei P, et al. (2020) Clinical efficacy of anakinra to mitigate CAR T-cell therapy-associated toxicity in large B-cell lymphoma. Blood Adv 4: 3123-3127. https://doi.org/10.1182/bloodadvances.2020002328
|
| [112] |
Gust J, Hay KA, Hanafi LA, et al. (2017) Endothelial activation and blood-brain barrier disruption in neurotoxicity after adoptive immunotherapy with CD19 CAR-T cells. Cancer Discov 7: 1404-1419. https://doi.org/10.1158/2159-8290.CD-17-0698
|
| [113] |
Santomasso BD, Park JH, Salloum D, et al. (2018) Clinical and biological correlates of neurotoxicity associated with CAR T-cell therapy in patients with B-cell acute lymphoblastic leukemia. Cancer Discov 8: 958-971. https://doi.org/10.1158/2159-8290.CD-17-1319
|
| [114] |
Morris EC, Neelapu SS, Giavridis T, et al. (2022) Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy. Nat Rev Immunol 22: 85-96. https://doi.org/10.1038/s41577-021-00547-6
|
| [115] |
Neelapu SS (2019) Managing the toxicities of CAR T-cell therapy. Hematol Oncol 37: 48-52. https://doi.org/10.1002/hon.2595
|
| [116] |
Hill JA, Li D, Hay KA, et al. (2018) Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy. Blood 131: 121-130. https://doi.org/10.1182/blood-2017-07-793760
|
| [117] | Barreto JN, Bansal R, Bansal A, et al. (2019) Infectious complications in patients receiving CD19-targeted CAR T cell therapy for relapsed/refractory B-cell malignancies. Open Forum Infect Dis 6: S415. |
| [118] |
Strati P, Varma A, Adkins S, et al. (2021) Hematopoietic recovery and immune reconstitution after axicabtagene ciloleucel in patients with large B-cell lymphoma. Haematologica 106: 2667-2672. https://doi.org/10.3324/haematol.2020.254045
|
| [119] |
Logue JM, Zucchetti E, Bachmeier CA, et al. (2021) Immune reconstitution and associated infections following axicabtagene ciloleucel in relapsed or refractory large B-cell lymphoma. Haematologica 106: 978-986. https://doi.org/10.3324/haematol.2019.238634
|
| [120] | Reinke JG, Schorr C, Lee KP (2026) Why are long-lived plasma cells long-lived?. Front Immunol 14: 1238097. https://doi.org/10.3389/fimmu.2026.1785563 |
| [121] |
Cordeiro A, Bezerra ED, Hirayama AV, et al. (2020) Late events after treatment with CD19-targeted chimeric antigen receptor modified T cells. Biol Blood Marrow Transplant 26: 26-33. https://doi.org/10.1016/j.bbmt.2019.08.003
|
| [122] |
Mikkilineni L, Kochenderfer JN (2021) CAR T cell therapies for patients with multiple myeloma. Nat Rev Clin Oncol 18: 71-84. https://doi.org/10.1038/s41571-020-0427-6
|
| [123] |
Chong EA, Melenhorst JJ, Lacey SF, et al. (2017) PD-1 blockade modulates chimeric antigen receptor (CAR)-modified T cells: Refueling the CAR. Blood 129: 1039-1041. https://doi.org/10.1182/blood-2016-09-738245
|
| [124] |
Hou AJ, Chen LC, Chen YY (2021) Navigating CAR-T cells through the solid-tumour microenvironment. Nat Rev Drug Discov 20: 531-550. https://doi.org/10.1038/s41573-021-00189-2
|
| [125] |
Micklethwaite KP, Gowrishankar K, Gloss BS, et al. (2021) Investigation of product-derived lymphoma following infusion of piggyBac-modified CD19 chimeric antigen receptor T cells. Blood 138: 1391-1405. https://doi.org/10.1182/blood.2021010858
|
| [126] |
Cappell KM, Kochenderfer JN (2023) Long-term outcomes following CAR T cell therapy: What we know so far. Nat Rev Clin Oncol 20: 359-371. https://doi.org/10.1038/s41571-023-00754-1
|
| [127] |
Ramakrishna S, Highfill SL, Walsh Z, et al. (2019) Modulation of target antigen density improves CAR T-cell functionality and persistence. Clin Cancer Res 25: 5329-5341. https://doi.org/10.1158/1078-0432.CCR-18-3784
|
| [128] |
Samur MK, Fulciniti M, Aktas Samur A, et al. (2021) Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with multiple myeloma. Nat Commun 12: 868. https://doi.org/10.1038/s41467-021-21177-5
|
| [129] |
Munshi NC, Anderson LD, Shah N, et al. (2021) Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med 384: 705-716. https://doi.org/10.1056/NEJMoa2024850
|
| [130] |
Turtle CJ, Hanafi LA, Berger C, et al. (2016) Immunotherapy of non-Hodgkin's lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor-modified T cells. Sci Transl Med 8: 355ra116. https://doi.org/10.1126/scitranslmed.aaf8621
|
| [131] |
Fry TJ, Shah NN, Orentas RJ, et al. (2018) CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med 24: 20-28. https://doi.org/10.1038/nm.4441
|
| [132] |
Hegde M, Mukherjee M, Grada Z, et al. (2016) Tandem CAR T cells targeting HER2 and IL13Rα2 mitigate tumor antigen escape. J Clin Invest 126: 3036-3052. https://doi.org/10.1172/JCI83416
|
| [133] |
Schneider D, Xiong Y, Wu D, et al. (2017) A tandem CD19/CD20 CAR lentiviral vector drives on-target and off-target antigen modulation in leukemia cell lines. J Immunother Cancer 5: 42. https://doi.org/10.1186/s40425-017-0246-1
|
| [134] |
Spiegel JY, Patel S, Muffly L, et al. (2021) 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 27: 1419-1431. https://doi.org/10.1038/s41591-021-01436-0
|
| [135] |
Tong C, Zhang Y, Liu Y, et al. (2020) Optimized tandem CD19/CD20 CAR-engineered T cells in refractory/relapsed B-cell lymphoma. Blood 136: 1632-1644. https://doi.org/10.1182/blood.2020005278
|
| [136] |
Di Stasi A, Tey SK, Dotti G, et al. (2011) Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med 365: 1673-1683. https://doi.org/10.1056/NEJMoa1106152
|
| [137] |
Diaconu I, Ballard B, Zhang M, et al. (2017) Inducible caspase-9 selectively modulates the toxicities of CD19-specific chimeric antigen receptor-modified T cells. Mol Ther 25: 580-592. https://doi.org/10.1016/j.ymthe.2017.01.011
|
| [138] |
Wang X, Chang WC, Wong CW, et al. (2011) A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells. Blood 118: 1255-1263. https://doi.org/10.1182/blood-2011-02-337360
|
| [139] |
Wu CY, Roybal KT, Puchner EM, et al. (2015) Remote control of therapeutic T cells through a small molecule-gated chimeric receptor. Science 350: aab4077. https://doi.org/10.1126/science.aab4077
|
| [140] |
Beatty GL, Haas AR, Maus MV, et al. (2014) Mesothelin-specific chimeric antigen receptor mRNA-engineered T cells induce anti-tumor activity in solid malignancies. Cancer Immunol Res 2: 112-120. https://doi.org/10.1158/2326-6066.CIR-13-0170
|
| [141] |
Zhao Z, Chen Y, Francisco NM, et al. (2018) The application of CAR-T cell therapy in hematological malignancies: Advantages and challenges. Acta Pharm Sin B 8: 539-551. https://doi.org/10.1016/j.apsb.2018.03.001
|
| [142] |
Billingsley MM, Singh N, Ravikumar P, et al. (2020) Ionizable lipid nanoparticle-mediated mRNA delivery for human CAR T cell engineering. Nano Lett 20: 1578-1589. https://doi.org/10.1021/acs.nanolett.9b04246
|
| [143] |
Qasim W, Zhan H, Samarasinghe S, et al. (2017) Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells. Sci Transl Med 9: eaaj2013. https://doi.org/10.1126/scitranslmed.aaj2013
|
| [144] |
Eyquem J, Mansilla-Soto J, Giavridis T, et al. (2017) Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature 543: 113-117. https://doi.org/10.1038/nature21405
|
| [145] |
Diorio C, Teachey DT, Grupp SA (2025) Allogeneic chimeric antigen receptor cell therapies for cancer: progress made and remaining roadblocks. Nat Rev Clin Oncol 22: 10-27. https://doi.org/10.1038/s41571-024-00959-y
|
| [146] |
Mock U, Nickolay L, Philip B, et al. (2016) Automated manufacturing of chimeric antigen receptor T cells for adoptive immunotherapy using CliniMACS prodigy. Cytotherapy 18: 1002-1011. https://doi.org/10.1016/j.jcyt.2016.05.009
|
| [147] |
Priesner C, Aleksandrova K, Esser R, et al. (2016) Automated enrichment, transduction, and expansion of clinical-scale CD62L+ T cells for manufacturing of gene therapy medicinal products. Hum Gene Ther 27: 860-869. https://doi.org/10.1089/hum.2016.091
|
| [148] |
Ghassemi S, Nunez-Cruz S, O'Connor RS, et al. (2018) Reducing ex vivo culture improves the antileukemic activity of chimeric antigen receptor (CAR) T cells. Cancer Immunol Res 6: 1100-1109. https://doi.org/10.1158/2326-6066.CIR-17-0405
|
| [149] |
Locke FL, Rossi JM, Neelapu SS, et al. (2020) Tumor burden, inflammation, and product attributes determine outcomes of axicabtagene ciloleucel in large B-cell lymphoma. Blood Adv 4: 4898-4911. https://doi.org/10.1182/bloodadvances.2020002394
|
| [150] |
Brudno JN, Natarajan V, Horick NK, et al. (2020) Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma. Nat Med 26: 270-280. https://doi.org/10.1038/s41591-019-0737-3
|
| [151] |
Oved JH, Barrett DM, Teachey DT (2019) Cellular therapy: Immune-related complications. Immunol Rev 290: 114-126. https://doi.org/10.1111/imr.12768
|
| [152] |
Hirayama AV, Gauthier J, Hay KA, et al. (2019) High rate of durable complete remission in follicular lymphoma after CD19 CAR-T cell immunotherapy. Blood 134: 636-640. https://doi.org/10.1182/blood.2019000905
|
| [153] |
Müller F, Hagen M, Wirsching A, et al. (2024) CD19 CAR-T cells for treatment-refractory autoimmune diseases: Results from the phase 1/2 CASTLE basket trial. Nat Med 32: 1142-1151. https://doi.org/10.1038/s41591-025-04185-6
|
| [154] |
Lickefett B, Chu L, Ortiz-Maldonado V, et al. (2023) Lymphodepletion—an essential but undervalued part of the chimeric antigen receptor T-cell therapy cycle. Front Immunol 14: 1303935. https://doi.org/10.3389/fimmu.2023.1303935
|
| [155] |
Locke FL, Ghobadi A, Jacobson CA, et al. (2019) Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): A single-arm, multicentre, phase 1-2 trial. Lancet Oncol 20: 31-42. https://doi.org/10.1016/S1470-2045(18)30864-7
|
| [156] |
Hay KA, Gauthier J, Hirayama AV, et al. (2019) Factors associated with durable EFS in adult B-cell ALL patients achieving MRD-negative CR after CD19 CAR T-cell therapy. Blood 133: 1652-1663. https://doi.org/10.1182/blood-2018-11-883710
|
| [157] |
Wobma H, Henderson LA, Duncan CN, et al. (2025) Treating and triggering hyperinflammation: Tackling hemophagocytic lymphohistiocytosis and HLH-like syndromes in the pediatric cell therapy and critical care setting. Front Oncol 15: 1631557. https://doi.org/10.3389/fonc.2025.1631557
|
| [158] | Wang H, Liu H, Shi Y, et al. (2026) LBS1:03 CTA313, CD19/BCMA dual targeted allo-CAR-T cell, durable remission in systemic lupus erythematosus following deep B-cell depletion, suggestive of immune-reset. Lupus Sci Med 13: e399. https://doi.org/10.1136/lupus-2026-el.399 |
| [159] | Hong M, Wang M, Zeng R, et al. (2026) PT4:02 Landmark long-term remission achieved with ICG318, a BCMA-CD19 armored CAR T-cell therapy in refractory systemic lupus erythematosus/lupus nephritis. Lupus Sci Med 13: e49. https://doi.org/10.1136/lupus-2026-el.49 |
| [160] |
Lin JK, Muffly LS, Spinner MA, et al. (2019) Cost effectiveness of chimeric antigen receptor T-cell therapy in multiply relapsed or refractory adult large B-cell lymphoma. J Clin Oncol 37: 2105-2119. https://doi.org/10.1200/JCO.18.02079
|
| [161] |
Santosa A, Tan TC (2026) CAR-T cell therapy for treatment-refractory rheumatic autoimmune diseases: A systematic review. RMD Open 12: e006417. https://doi.org/10.1136/rmdopen-2025-006417
|
| [162] |
Sarkar RR, Gloude NJ, Schiff D, et al. (2019) Cost-effectiveness of chimeric antigen receptor T-cell therapy in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia. J Natl Cancer Inst 111: 719-726. https://doi.org/10.1093/jnci/djy193
|
| [163] | Arruda LCM, Malmegrim KC, Lima-Júnior JR, et al. (2016) Resetting the immune response after autologous hematopoietic stem cell transplantation for autoimmune diseases. Curr Res Transl Med 64: 107-113. https://doi.org/10.1016/j.retram.2016.03.004 |
| [164] |
Kazmi M, Muraro PA, Mehra V, et al. (2025) Autologous haematopoietic stem cell transplantation for multiple sclerosis in the UK: A 20-year retrospective analysis of activity and haematological outcomes from the British Society of Blood and Marrow Transplantation and Cellular Therapy (BSBMTCT). Br J Haematol 207: 977-991. https://doi.org/10.1111/bjh.20199
|
| [165] |
Li J, Guo Q, Li L, et al. (2026) CAR-T and BiTE: New horizons in the treatment of rheumatic autoimmune diseases. Front Immunol 17: 1747777. https://doi.org/10.3389/fimmu.2026.1747777
|
| [166] |
Goebeler ME, Bargou RC (2020) T cell-engaging therapies—BiTEs and beyond. Nat Rev Clin Oncol 17: 418-434. https://doi.org/10.1038/s41571-020-0347-5
|
| [167] |
Düsing C, Györfi AH, Stütz AN, et al. (2026) Bispecific T cell engagers for treatment-refractory autoimmune connective tissue diseases. Nat Med 32: 1530-1542. https://doi.org/10.1038/s41591-026-04238-4
|
| [168] |
Gao W, Yu J, Sun Y, et al. (2025) Adverse events in the nervous system associated with blinatumomab: A real-world study. BMC Med 23: 72. https://doi.org/10.1186/s12916-025-03913-6
|
| [169] |
Lewis G, Chan NLS, Frank B, et al. (2025) Anti-CD19/CD20 bispecific antibody with dual Fc domains mediates enhanced effector functions and durable depletion of memory B cells in vivo. Sci Rep 15: 31563. https://doi.org/10.1038/s41598-025-16461-z
|
 allergy-10-03-012-s001.pdf |
 |
Figures(2) / Tables(2)
Cromwel Tepap Zemnou, Ramelle Ngakam. Chimeric antigen receptor T cells in autoimmune diseases and allergy: From bench to bedside[J]. AIMS Allergy and Immunology, 2026, 10(3): 143-183. doi: 10.3934/Allergy.2026012
DownLoad: