Table 1.

CAR-T cell-derived immunotherapy in preclinical models of AIDs.

CARs/generations	Construction of specific T cells or Tregs	Disease model	Specific autoantigen	Outcome	Reference
Dsg3 CAAR-T cells/2nd	Human T cells were engineered to express a CAAR that consisted of the PV autoantigen, Dsg3, fused to CD137-CD3ζ signaling domains	PV	Dsg3	Effective for PV relief, obviously decreased Dsg3 serum autoantibody titers	Ellebrecht et al. [42]
CD19-targeted CAR-T cells/2nd	CD8+ T cells were modified to express CD19-targeted CARs with CD28-CD3ζ signaling domains	Lupus	CD19	Eliminated autoantibody production, reversed disease phenotype, and prolonged survival time	Kansal and Richardson [45]
287-CAR-T cells/2nd or 3rd	CD8+ T cells were modified to express monoclonal antibody 287 CARs (287-CARs) harboring CD28-CD3ζ or CD28-CD137-CD3ζ signaling domains	T1D	I-Ag7-B:9-23 (R3) complex	Delayed but did not prevent the onset of T1D	Zhang et al. [49]
Insulin-specific CAR-Tregs/2nd	CD4+ T cells were transduced with retroviral particles encoding the CAR plasmid including Foxp3 to convert CD4+ T cells into Tregs	T1D	Insulin	Failed to prevent spontaneous diabetes	Tenspolde et al. [54]
MOG CAR-Tregs/2nd	CD4+ T cells transduced to Tregs expressing CARs with MOG, the FoxP3 gene, and CD28-CD3ζ signaling domains	MS	MOG	Inhibited EAE demonstrated as reduced cytokine expression and diminished disease symptoms	Fransson et al. [55]
TNP-TPCR Tregs	TNP-TPCR Tregs were isolated from transgenic mice expressing the TNP-specific chimeric receptor under the CD2 promoter	Colitis	TNP	Alleviated acute TNBS colitis	Elinav et al. [56]
CEA-specific CAR-Tregs/2nd	CD4+CD25+ Tregs were transduced with the CEA-specific SCA431 CAR that was fused to CD28-CD3ζ signaling domains	Colitis and colorectal cancer	CEA	Ameliorated colitis and prevented development of colitis-associated colorectal cancer	Blat et al. [57]

PV: pemphigus vulgaris; T1D: type I diabetes; Dsg3: desmoglein 3; MS: multiple sclerosis; MOG: myelin oligodendrocyte glycoprotein; EAE: encephalomyelitis; TPCR: tripartite chimeric receptor; TNP: 2,4,6-trinitrophenol; TNBS: 2,4,6-trinitrobenzenesulphonic acid; CEA: carcinoembryonic antigen.