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

Table 2. Ongoing clinical trials of CAR‑T cell therapy for MG
Trial registration Target Start date Study design Overview of the study Clinical Sample Clinical
number phases size progress
NCT05828225 CD19 April 30, 2023 Non-randomized The primary objective is to evaluate I 9 Recruit
controlled trials the safety of CD19 CAR-T in patients patients
with refractory MG and to evaluate the
pharmacokinetics of CD19 CAR-T in
patients.
NCT04146051 BCMA December 4, Randomized Application of DesCAR-Tes-08 CAR-T IIb 30 Recruit
2019 controlled trials cells in generalized MG patients
NCT05451212 MuSK-specific November 23, Non-randomized A phase 1, open-label, safety and I 24 Recruit
B cells 2022 controlled trials dose-finding study of autologous patients
muscle-specific tyrosine kinase
chimeric autoantibody receptor T
cells (MuSK-CAART) in subjects with
anti-MuSK antibody-positive MG
NCT04561557 BCMA September 22, Non-randomized An open-label clinical trial evaluating I 18 Recruit
2020 controlled trials the safety and efficacy of CT103A cells patients
in the treatment of relapsed/refractory
antibody-related idiopathic inflammatory
diseases of the nervous system
Abbreviations: MG: Myasthenia gravis; CAR: Chimeric antigen receptor.

cells, and in vitro cytotoxicity tests using cloned CD4+ stimulation, enabling them to suppress effector T cells even
T cells as target cells revealed that DR1-CII CAR-T cells in the absence of the co-stimulatory factor B7-CD28. When
effectively detect and kill CII-specific autoreactive CD4+ Tregs carrying CRs were transplanted into wild-type mice
T cells. Treatment with DR1-CII CAR-T cells considerably with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced
reduced the CD4+ T cell response specific to CII, blocked colitis, a significant increase in their survival rate was
autoantibody formation, and reduced disease severity in observed. Interestingly, although TNP-specific CR-Tregs
B6 DR1 mice with induced autoimmune arthritis. These were unable to suppress dextran sulfate sodium (DSS)-
findings suggest that HLA-DR CAR-T cells hold promise induced colitis, administering a small amount of TNBS led
as highly targeted therapeutic options for ADs. 72 to the cure of the DSS colitis mouse model. Within a few
3.7. Application of CAR-T cells in the treatment of hours of colitis induction, in vivo imaging of transplanted
ulcerative colitis CR-carrying Tregs revealed their tendency to migrate to
locations of TNBS-induced colonic mucosal injury. This
The significance of Tregs in maintaining the integrity of evidence suggests that Tregs accumulate at the sites of colitis
the intestinal mucosa in ulcerative colitis, an IBD, has inflammation owing to a specific redirecting mechanism
been extensively demonstrated. Human Foxp3 is one of that differs from that of pathogenic lymphocytes. These
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the key transcription factors controlling the development Tregs were able to suppress effector T cells in a non-MHC-
and function of Tregs, and mutations in the Foxp3 gene
can lead to severe ADs, including IBD. Similarly, mice restricted and non-co-stimulatory-dependent manner.
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with deficient Treg activity are prone to severe colitis. Thus, they significantly alleviated colitis.
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To alleviate colitis, Tregs may reduce the proliferation Carcinoembryonic antigen (CEA) is overexpressed in
of effector T cells and the release of pro-inflammatory human colitis and colorectal cancer. Blat et al. utilized
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cytokines and block components of the innate immune CEA-specific CAR-Tregs to treat a CEA-colitis animal
system. 76 model. Following systemic treatment, CEA-CAR-Tregs
Elinav et al. successfully generated transgenic mice with aggregated in the colons of afflicted mice and demonstrated
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T cells expressing chimeric receptors (CR). These receptors, a reduction in colitis symptoms compared to control
comprising antibody-variable regions for recognition Tregs. Furthermore, the CEA-CAR-Tregs hindered the
along with T-cell stimulation and co-stimulation domains, development of colorectal cancers in an azoxymethane-
are designed to specifically target the predetermined model DSS model. These results suggest a high potential for CEA-
antigen, 2,4,6-trinitrophenol (TNP). Furthermore, TNP- CAR-Tregs in the treatment of both ulcerative colitis and
specific CR-Tregs can be activated through external TNP colorectal cancer. 78

Volume 3 Issue 2 (2024) 8 doi: 10.36922/gpd.2851