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Gene & Protein in Disease Review of CAR-T in ADs

Table 1. Ongoing clinical trials of CAR‑T cell therapy in SLE
Trial registration Target Start date Study design Overview of the study Clinical Sample Clinical
number phases size progress
NCT03030976 CD19 March 2017 Non-randomized To evaluate cellular immunotherapy I 5 Unknown
controlled trials using CD19-targeting CAR-engineered
T cells in patients with CD19+B-cell
SLE
NCT05765006 CD19 February Non-randomized A phase I dose-escalation study I 24 Recruit patients
2023 controlled trials evaluating the safety, tolerability,
pharmacokinetics (PK), and
pharmacodynamics (PD) of relma-cel
in subjects with moderately to severely
active SLE
NCT05030779 CD19-BCMA September Non-randomized A clinical trial of the safety and efficacy I 9 Recruit patients
2021 controlled trials of CD19/BCMA CAR-T cells in
patients with refractory SLE
NCT05869955 CD19 July 2023 Non-randomized A Phase 1, multicenter, open-label I 43 Recruit patients
controlled trials study of CC-97540 (BMS-986353)
targeting CD19’s next-T CAR T cells in
patients with severe refractory SLE
NCT05474885 CD19-BCMA April 2022 Non-randomized BCMA-CD19 cCAR T-cell therapy for I 15 Recruit patients
controlled trials relapsed/refractory SLE
NCT05798117 CD19 February Non-randomized An open-label, multicenter, phase 1/2 I 27 Recruit patients
2023 controlled trials study to evaluate the safety, efficacy,
and cytokinetics of YTB323 in patients
with severe refractory SLE
NCT05858684 CD19-BCMA May 2023 Non-randomized Dual-target CAR-T cell therapy in I 18 Recruit patients
controlled trials patients with refractory SLE
NCT05930314 CD19 June 2023 Non-randomized Dual-targeted CAR-T cell therapy for I 12 Recruit patients
controlled trials patients with refractory SLE
NCT05846347 CD19-BCMA May 2023 Non-randomized Phase I clinical study of GC012F I 15 Recruit patients
controlled trials injection in the treatment of refractory
SLE
Abbreviations: SLE: Systemic lupus erythematosus; CAR: Chimeric antigen receptor.

3.3. Application of CAR-T in the treatment of Dsg3 CAAR-T cells could multiply, survive, and precisely
pemphigus vulgaris (PV) destroy Dsg3-specific B cells. At present, a phase 1 open-
PV is an autoimmune blistering disorder that can prove label dosage and safety trial utilizing Dsg3-CAAR-T cells
fatal in the presence of autoantibodies targeting the cell is underway in patients with active anti-DSG3, mucosal-
49
adhesion protein Dsg3. Studies indicate that short-lived dominant PV (NCT04422912). These findings highlight
the potential of CAAR-T cells as an effective and adaptable
plasma cells are the source of autoantibodies in PV. method for specifically targeting self-reactive B cells in
50
Therefore, targeting and eliminating anti-Dsg3-specific antibody-mediated ADs. 53
antibody-secreting B cells offers a promising avenue for
treating PV without causing overall immunosuppression. 51 3.4. Application of CAR-T in the treatment of MG
PV and CAAR-T cells in antibody-mediated ADs can In MG, self-antibodies target proteins at the neuromuscular
be created to selectively drive T cells to destroy self-reactive junction, resulting in persistent, variable, and sometimes
B lymphocytes, guided by B cell receptor specificity. debilitating weakness and muscle exhaustion. Prevalent
54
Ellebrecht et al. engineered human T cells to produce pathogenic antibodies linked with MG include anti-
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CAAR comprising the PV self-antigen desmoglein 3 linked AChR, anti-MuSK, and anti-LRP4 antibodies. However,
to CD137-CD3 signaling domains. They discovered that there remains a considerable unmet medical need for
Dsg3 CAAR-T cells demonstrated selective cytotoxicity MG patients who are currently unresponsive to standard
in vitro against cells expressing the anti-Dsg3 B cell immunosuppressive therapy or experience severe adverse
receptor. They also discovered that in animal models, effects. 55

Volume 3 Issue 2 (2024) 6 doi: 10.36922/gpd.2851