CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus

Mougiakakos, Dimitrios; Krönke, Gerhard; Völkl, Simon; Kretschmann, Sascha; Aigner, Michael; Kharboutli, Soraya; Boeltz, Sebastian; Manger, Bernhard; Mackensen, Andréas; Schett, Georg

doi:10.1056/nejmc2107725

Cited by 285 publications

(174 citation statements)

References 5 publications

Supporting

Mentioning

159

Contrasting

Unclassified

Order By: Relevance

“…B-cell depletion therapy, such as rituximab, may be a good therapeutic option. As described in SLE, belimumab, daratumumab, or CD19-targeted chimeric antigen receptor T-cell therapy might also be useful ( 32 , 33 ). For AD associated with CTLA4 deficiency, it is necessary to decide the timing of abatacept or HSCT in considering possible treatment-refractory or potential additional AD, as described in a retrospective world survey ( 9 ).…”

Section: Discussionmentioning

confidence: 99%

Clinical Courses of IKAROS and CTLA4 Deficiencies: A Systematic Literature Review and Retrospective Longitudinal Study

et al. 2022

View full text Add to dashboard Cite

IKAROS and CTLA4 deficiencies are inborn errors of immunity and show similar clinical phenotypes, including hypogammaglobulinemia and autoimmune diseases (ADs). However, the differences in clinical features and pathogenesis of these are not fully understood. Therefore, we performed systematic literature reviews for IKAROS and CTLA4 deficiencies. The reviews suggested that patients with IKAROS deficiency develop AD earlier than hypogammaglobulinemia. However, no study assessed the detailed changes in clinical manifestations over time; this was likely due to the cross-sectional nature of the studies. Therefore, we conducted a retrospective longitudinal study on IKAROS and CTLA4 deficiencies in our cohort to evaluate the clinical course over time. In patients with IKAROS deficiency, AD and hypogammaglobulinemia often develop in that order, and AD often resolves before the onset of hypogammaglobulinemia; these observations were not found in patients with CTLA4 deficiency. Understanding this difference in the clinical course helps in the clinical management of both. Furthermore, our results suggest B- and T-cell-mediated ADs in patients with IKAROS and CTLA4 deficiencies, respectively.

show abstract

Section: Discussionmentioning

confidence: 99%

Clinical Courses of IKAROS and CTLA4 Deficiencies: A Systematic Literature Review and Retrospective Longitudinal Study

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Whether the choice of optimal signal domain composition or the addition of internal autocrine cytokine release and suicide switches depend on the tumor entity, qualitatively or quantitatively on the target antigen or on other factors, requires further investigation for other malignancies and constructs-such as BCMA CARs in MM [32]. However, while these artificial receptors are mainly considered a breakthrough in tumor therapy, their potential for application in other disease settings, exemplarily infectious [52] or autoimmune [53,54], should also be mentioned.…”

Section: General Aspects Of Car Constructsmentioning

confidence: 99%

Adoptive Cellular Therapy for Multiple Myeloma Using CAR- and TCR-Transgenic T Cells: Response and Resistance

Füchsl

Krackhardt

2022

Cells

View full text Add to dashboard Cite

Despite the substantial improvement of therapeutic approaches, multiple myeloma (MM) remains mostly incurable. However, immunotherapeutic and especially T cell-based approaches pioneered the therapeutic landscape for relapsed and refractory disease recently. Targeting B-cell maturation antigen (BCMA) on myeloma cells has been demonstrated to be highly effective not only by antibody-derived constructs but also by adoptive cellular therapies. Chimeric antigen receptor (CAR)-transgenic T cells lead to deep, albeit mostly not durable responses with manageable side-effects in intensively pretreated patients. The spectrum of adoptive T cell-transfer covers synthetic CARs with diverse specificities as well as currently less well-established T cell receptor (TCR)-based personalized strategies. In this review, we want to focus on treatment characteristics including efficacy and safety of CAR- and TCR-transgenic T cells in MM as well as the future potential these novel therapies may have. ACT with transgenic T cells has only entered clinical trials and various engineering strategies for optimization of T cell responses are necessary to overcome therapy resistance mechanisms. We want to outline the current success in engineering CAR- and TCR-T cells, but also discuss challenges including resistance mechanisms of MM for evading T cell therapy and point out possible novel strategies.

show abstract

“…Although limited by numbers, several reports have shown successful transfer of Ag-specific Tregs in mice recapitulating RA, suggesting their therapeutic potentials in systemic autoimmune diseases of rheumatologic fields as in other diseases ( 69 70 ). Beyond CAR-Treg therapies, one recent report has demonstrated that infusion of CAR-T cells targeting CD19-expressing cells after preconditioning for lymphodepletion can induce dramatic remission in a refractory SLE patient ( 71 ). This result suggests that the CAR system has potential to deplete specific autoreactive cell populations selectively in autoimmune diseases as it does in cancers.…”

Section: Tregsmentioning

confidence: 99%

Recent Advances in Cell Therapeutics for Systemic Autoimmune Diseases

Park

Kwok

2022

Immune Netw

View full text Add to dashboard Cite

Systemic autoimmune diseases arise from loss of self-tolerance and immune homeostasis between effector and regulator functions. There are many therapeutic modalities for autoimmune diseases ranging from conventional disease-modifying anti-rheumatic drugs and immunosuppressants exerting nonspecific immune suppression to targeted agents including biologic agents and small molecule inhibitors aiming at specific cytokines and intracellular signal pathways. However, such current therapeutic strategies can rarely induce recovery of immune tolerance in autoimmune disease patients. To overcome limitations of conventional treatment modalities, novel approaches using specific cell populations with immune-regulatory properties have been attempted to attenuate autoimmunity. Recently progressed biotechnologies enable sufficient in vitro expansion and proper manipulation of such ‘tolerogenic’ cell populations to be considered for clinical application. We introduce 3 representative cell types with immunosuppressive features, including mesenchymal stromal cells, Tregs, and myeloid-derived suppressor cells. Their cellular definitions, characteristics, mechanisms of immune regulation, and recent data about preclinical and clinical studies in systemic autoimmune diseases are reviewed here. Challenges and limitations of each cell therapy are also addressed.

show abstract

CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus

Cited by 285 publications

References 5 publications

Clinical Courses of IKAROS and CTLA4 Deficiencies: A Systematic Literature Review and Retrospective Longitudinal Study

Clinical Courses of IKAROS and CTLA4 Deficiencies: A Systematic Literature Review and Retrospective Longitudinal Study

Adoptive Cellular Therapy for Multiple Myeloma Using CAR- and TCR-Transgenic T Cells: Response and Resistance

Recent Advances in Cell Therapeutics for Systemic Autoimmune Diseases

Contact Info

Product

Resources

About