. 2021 Mar 29;12:657768. doi: 10.3389/fimmu.2021.657768

Table 6.

T cell therapies for the treatment of inflammatory disease.

T cell Therapeutic	Disease Model	Extracellular Domain	Trans-membrane Domain	Intracellular Domain and Payload	T Cell Subset Utilized as Therapeutic	Outcomes	Ref.
CD4⁺ A2-CAR-Tregs	Transplant Rejection	Anti-HLA-A2 scFv (Clone BB7.2)	CD28	CD28-CD3ζ	Human CD4⁺ CD45RO^low CD45RA^high CD25^high Tregs	5-10 x10⁵ human CD4⁺ A2-CAR-Tregs suppressed xenogeneic GVHD in NSG mice when administered with effector HLA-A2⁺ T cells.	(224)
CD4⁺ A2-CAR-Tregs	Transplant Rejection	Anti-HLA-A2 scFv (phage display library)	CD28	CD28-CD3ζ	Human CD4⁺ CD25⁺ Treg	1 x10⁶ human CD4⁺ A2-CAR-Tregs prevented human HLA-A2⁺ skin graft rejection in BRG mice when administered with HLA-A2^- effector T cells.	(225)
CD4⁺ A2-CAR-Tregs	Transplant Rejection	Anti-HLA-A2 scFv (phage display library)	CD8	CD28-CD3ζ	Human CD8⁻ CD4⁺ CD25^high CD127^low Tregs	1 x10⁶ human CD4⁺ A2-CAR-Tregs prevented human HLA-A2⁺ skin graft rejection in NRG mice when administered with HLA-A2^- effector T cells.	(226)
CD4⁺ MOG-CAR-FOXP3-T cells	Multiple Sclerosis	Anti-MOG scFv (Clone 8.18 C5)	CD3	CD3ζ-CD28 Payload FOXP3	Murine CD4⁺ T cells	1 x10⁵ murine CD4⁺ MOG-CAR-FOXP3-T cells suppressed MOG_35-55 induced EAE in C57BL/6 mice when administered after disease onset.	(36)
CD4⁺ MOG- or MBP-CAR-Tregs	Multiple Sclerosis	Anti-MOG or MBP scFv (phage display library)	CD28	CD28-CD3ζ	Human CD4⁺ CD25^high and CD127^low Tregs	1 x10⁶ human CD4⁺ MOG- and MBP-CAR-Tregs mixed 50:50 suppressed MOG_35-55-induced EAE in C57BL/6 mice when administered 7 days after disease induction.	(227)
CD4⁺ TNP-CAR-Tregs	Colitis	Anti-TNP (Clone Sp6)	CD28	CD28-FcRγ	Murine CD4⁺ CD25^high Tregs from TNP-CAR Tg mice	1 x10⁶ murine CD4⁺ TNP-CAR-Tregs suppressed TNBS induced colitis in BALB/c or C57BL/6 mice when administered 16 hours after disease induction.	(228)
CD4⁺ Insulin-CAR-FOXP3-T cells	Type 1 Diabetes	Anti-Insulin scFv (phage display library)	CD8	CD28-CD3ζ Payload FOXP3	Murine CD4⁺ T cells	2.5 x10⁶ murine CD4⁺ Insulin-CAR-FOXP3-T cells failed to prevent the onset of diabetes in prediabetic NOD mice.	(37)
CD4⁺ FVIII-CAR-Tregs	Anti-FVIII responses in Hemophilia A	Anti-FVIII scFv (phage display library)	CD28	CD28-CD3ζ	Human CD4⁺ CD25^high CD127^low CD45RA⁺ Tregs	1-2 x10⁶ human CD4⁺ FVIII-CAR-Tregs suppressed the formation of FVIII antibodies in FVIII exon 16 knockout x HLA-DRB1 mice when administered on the same day as FVIII sensitization.	(229)
CD4⁺ FVIII-CAR-T cells	Anti-FVIII responses in Hemophilia A	Anti-FVIII scFv (phage display library)	CD28	CD28-CD137-CD3ζ Payload FOXP3	Murine CD4⁺ T cells	4 x10⁵ murine CD4⁺ FVIII-CAR-FOXP3-T cells suppressed the formation of FVIII antibodies in mice FVIII exon 16 knockout mice receiving FVIII gene therapy.	(230)
CD4⁺ CEA-CAR-Tregs	Allergic Disease	Anti-CEA scFv (Clone SCA431)	CD4	CD28-CD3ζ	Murine CD4⁺ CD25⁺ Tregs from CEA-CAR Tg mice	1 x10⁶ murine CD4⁺ CEA-CAR-Tregs suppressed hyper-reactivity, mucus production, and eosinophilia in CEA Tg mice with OVA induced experimental asthma when administered 7 days after the first sensitization.	(231)
CD4⁺ UniCAR- Tregs	Tumor Rejection Suppression	Anti-E5B9 scFv (Clone 5B9) + anti-PSCA-E5B9	CD28	CD28-CD3ζ or CD137-CD3ζ	Human CD4⁺ CD25⁺ CD127^dim CD45RA⁺ Tregs	1 x10⁶ human CD4⁺ PSCA-UniCAR-Tregs with the CD137-CD3ζ signaling domains suppressed the rejection of PC3-PSCA tumors in NMRI^nu/nu mice when administered alongside PSCA-CAR-T cells.	(232)
CD4⁺ FITC-CAR-Tregs	Transplant Rejection	Anti-FITC scFv (Clone 1X9Q) + anti-H-2^d-FITC	CD28	CD28-CD3ζ	Murine CD4⁺ CD25^high GFP⁺ Tregs from FoxP3^luc/GFP mice	1.5 x10⁶ murine CD4⁺ anti-H-2^d-Fitc-CAR-Tregs increased H-2^d islet grafts survival in C57BL/6 (H-2^b) recipients.	(233)
CD8⁺ A2-CAR-Tregs	Transplant Rejection	Anti-HLA-A2 scFv (Clone BB7.2)	CD28	CD28-CD3ζ	Human CD8⁺ CD45RC^low Tregs	1.5-5 x10⁶ human CD8⁺ A2-CAR-Tregs prevented human HLA-A2⁺ skin graft rejection in NRG mice when administered with HLA-A2^- effector T cells.	(234)
CD4⁺ MBP_89-101-I-As- CAAR-Tregs	Type 1 Diabetes	I-As-MBP_89-101	I-As	CD3ζ	Murine CD4⁺ CD25⁺ Tregs from MBP_89-101-IA^s-ζ Tg mice	1 x10⁶ murine CD4⁺ MBP_89-101-I-As-CAAR-Tregs suppressed MBP_89-101 induced EAE in SJL mice when administered before or after disease onset.	(235)
CD4⁺ OVA-BAR-Tregs	Allergic Disease	Full-length OVA	CD28	CD28-CD3ζ	Murine TGF-β induced CD4⁺ Tregs or human CD4⁺ CD25^high CD127^low Tregs	5 x10⁶ murine or 1 x10⁶ human CD4⁺ OVA-BAR-Tregs protected BALB/c mice from OVA induced anaphylaxis. In addition, five million murine CD4⁺ OVA-BAR-Tregs suppressed anti-OVA IgE mast cell mediated anaphylaxis.	(236)
CD4⁺ FVIII-BAR-Tregs	Anti-FVIII responses in Hemophilia A	FVIII A2 and C2 domains	CD28	CD28-CD3ζ	Human CD4⁺ CD25^high CD127^low Tregs	1-2 x10⁶ human CD4⁺ FVII-BAR-Tregs suppressed the formation of FVIII antibodies in FVIII exon 16 knockout mice when administered before and after sensitization.	(237)
CD4⁺ OVA-TCR-Tregs or OVA-TCR-FOXP3-T cells	Rheumatoid Arthritis	OVA-specific TCR α and β	TCR α and β chains	TCR α and β chains Payload FOXP3	Murine CD4⁺ CD25⁺ Tregs	1.5 x10⁶ murine CD4⁺ OVA-TCR-Tregs or OVA-TCR-FOXP3-T cells suppressed methylated BSA induced arthritis in C57BL/6 mice following a rechallenge with methylated BSA+ OVA.	(238)
CD4⁺ MBP-TCR-Tregs	Multiple Sclerosis	MBP_85-99-specific TCR α and β	TCR α and β chains	TCR α and β chains	Human CD4⁺ CD25^high CD127^low Tregs	2 x10⁶ human CD4⁺ MBP-TCR-Tregs suppressed MOG_35-55 induced EAE in HLA-DR15 Tg mice when administered 7 days after disease induction.	(239)
CD4⁺ FVIII-TCR-Tregs	Anti-FVIII responses in Hemophilia A	FVIII_2191-2220 -specific TCR α and β	TCR α and β chains	TCR α and β chains	Human CD4⁺ CD25^high CD127^low Tregs	1-2 x10⁶ human CD4⁺ FVIII-TCR-Tregs suppressed FVIII antibody formation in FVIII exon 16 knockout mice crossed to human HLA-DRB1 mice.	(240)
CD8⁺ CD19-CAR-T cells	Systemic Lupus Erythematosus	Anti-CD19 scFv (Clone 1D3)	CD28	CD28-CD3ζ	Murine CD8⁺ T cells	1 x10⁶ murine CD8⁺ CD19-CAR-T cells suppressed SLE when administered before or after the development of disease in MRL-lpr and MZB/w mice, respectively.	(241)
CD8⁺ FcϵRIα-CAR-T cells	Allergic Diseases	FcϵRIα and reduced affinity muteins	CD3ζ	CD3ζ	Human CD8⁺ T cells	Human CD8⁺ FcϵRIα-CAR-T cells killed cells expressing transmembrane IgE.	(242)
CD8⁺ Anti-InsB_9-23-I-A^g7-CAR-T cells	Type 1 Diabetes	Anti-InsB_9-23-I-A^g7 scFv (clone mAb287)	CD28	CD28-CD3ζ or CD28-CD137-CD3ζ	Murine CD8⁺ T cells	3-5 x10⁶ murine CD8⁺ Anti-InsB_9-23-I-A^g7-CAR-T cells suppressed the development of diabetes when transferred to prediabetic NOD mice.	(243)
CD8⁺ InsB_15-23-β2m-CAAR-T cells	Type 1 Diabetes	InsB_15-23-β2m	CD3ζ	CD3ζ	Murine CD8⁺ T cells	1 x10⁷ murine CD8⁺ InsB_15-23-β2m-CAAR-T cells suppressed the development of diabetes when transferred to prediabetic NOD mice.	(244)
DSG3-CAAR-T cells	Pemphigus Vulgaris	Dsg3 extracellular domains 1-3, 1-4 or 1-5	CD8	CD137-CD3ζ	Human T cells	Human Dsg3-CAAR-T cells suppressed Dsg3-specific hybridoma driven GVHD in NSG mice.	(245)
MuSK-CAAR-T cells	Myasthenia Gravis	MuSK extracellular domain	N/A	CD137-CD3ζ	Human T cells	Human MuSK-CAAR-T cells suppressed the proliferation of MuSK-specific B cells in NSG mice.	(246)