TABLE 1.
Pre-clinical studies using CAR Tregs.
| Disease | Antigen specificity | Main results | References |
|---|---|---|---|
| Transplantation | |||
| GvHD | HLA-A2 | Human A2-CAR-Tregs were superior to irrelevant CAR-Tregs to prevent GvHD. | MacDonald et al. (2016) |
| GvHD and skin transplant | HLA-A2 | Human A2-CAR-Tregs prevented A2-expressing human skin graft rejection and prevented GvHD | Noyan et al. (2017) |
| Skin transplant | HLA-A2 | Human A2-CAR-Tregs prevented A2-expressing human skin graft rejection | Boardman et al. (2017) |
| GvHD and skin transplant | HLA-A2 | Human A2-CAR-Tregs prevented A2-expressing human skin graft rejection and prevented GvHD | Dawson et al. (2019) |
| Skin transplant | HLA-A2 | Mouse A2-CAR-Tregs delayed skin rejection, decreased donor-specific antibodies formation and A2-specific B cells formation, but only in unsensitized mice | Sicard et al. (2020) |
| Heart transplant | HLA-A2 | Mouse A2-CAR-Tregs prolonged the survival of heterotopic heart transplants | Wagner et al. (2022) |
| GvHD, islet and skin | Universal CAR | Mouse mAb-CAR-Tregs could prevent GvHD, prolong survival of islet allografts and secondary skin allografts | Pierini et al. (2017) |
| GvHD | HLA-A2 | Human A2-CAR-Tregs modified to overexpress Foxp3 were stable under proinflammatory conditions and had a survival advantage under IL-2 deprived conditions and could prevent human A2+ PBMC engraftment in humanized mouse model | Henschel et al. (2023) |
| Autoimmune diseases | |||
| Type 1 diabetes | Insulin B peptide-MHC class II | Mouse CAR-Tregs prevented adoptive transfer diabetes by BDC2.5 T cells in immunodeficient NOD mice and prevented spontaneous diabetes in wild type NOD mice | Spanier et al. (2023) |
| Type 1 diabetes | Insulin B peptide-MHC class II | Mouse InsB:R3-CAR-Tregs protected against spontaneous diabetes in NOD.CD28−/− mice | Obarorakpor et al. (2023) |
| Type 1 diabetes | Insulin B | Mouse effector T cells converted to Tregs using insulin-specific Foxp3+ CARs. Long-lived in diabetic mice | Tenspolde et al. (2019) |
| Colitis | TNP | Mouse TNP-CAR-Tregs improved colitis | Elinav et al. (2008) |
| Elinav et al. (2009) | |||
| Colitis | CEA | Mouse CEA-CAR-Tregs improved colitis | Blat et al. (2014) |
| Colitis | Flagellin | Human FliC-CAR-Tregs promoted the establishment of colon-derived epithelial cell monolayers and had a preferential migration to the colon | Boardman et al. (2023) |
| Multiple sclerosis | MOG (myelin oligodendrocyte glycoprotein) | Engineered mouse MOG-CAR-Tregs suppressed autoimmune encephalomyelitis better than non-specific Tregs | Fransson et al. (2012) |
| Vitiligo | GD3 (ganglioside D3) | Mouse GD3-CAR Tregs delayed depigmentation compared to untransduced Tregs | Mukhatayev et al. (2020) |
| Others | |||
| Alzheimer | Beta-Amyloid | Mouse beta-amyloid-CAR-Tregs were suppressive in vitro | Saetzler et al. (2023) |
| Asthma | CEA | Mouse CEA-CAR-Tregs reduced airway hyper-reactivity and diminished eosinophilic airway inflammation | Skuljec et al. (2017) |
| Hemophilia A | FVIII | Mouse FVIII-CAR-Tregs suppressed the proliferation of FVIII-specific T cells and suppress the recall antibody response | Yoon et al. (2017) |
| Hemophilia A | FVIII | Mouse CD4+ cells lentivirally transduced to express Foxp3 and FVIII-CAR. Promote FVIII tolerance | Fu et al. (2020) |