Table 2.
Strategies that delay or prevent diabetes in nonobese diabetic mice (2005–present).
| Agent | Details | Diabetes incidence | Ref. | ||
|---|---|---|---|---|---|
|
Control (%) |
Treated (%) |
Age (weeks) |
|||
| G-CSF | 200 µg/kg sc. daily for 5 days at 4, 8, 12 and 16 weeks | 75 | 8 | 30 | [149] |
| Myeloid progenitors expressing proinsulin | Generated in GM-CSF and TGF-β from bone marrow of NOD mice expressing Ins2 under the control of a class II MHC promoter; 2 × 106 cells iv. at 4 weeks | 83 | 33 | 34 | [150] |
| FTY720 | Sphingosine-1-phosphate analog; 1 mg/kg by oral gavage 5-times/week at 23–37 weeks | 78 | 0 | 37 | [151] |
| Altered peptide ligand of IGRP206–214 | 100 µg NRP-I4 ip. every 2 weeks at 4–8 weeks and every 3 weeks thereafter | 60 | 0 | 30 | [152] |
| Anti-PSGL-1 | Apoptosis-inducing anti-PSGL-1 (TAB4); 50 µg ip. at 8, 9, 10, 18, 19 and 20 weeks | 83 | 29 | 27 | [153] |
| GAD65260–279 (an ignored determinant) | Also known as GADp18; 100 µg in IFA at 12 weeks and also 10 days later | 93 | 27 | 45 | [154] |
| Probiotic bacteria | VSL#3 (3 × 1011 viable lyophilized bacteria/g); 3 mg by oral gavage 3-times/week at 4–32 weeks | 81 | 21 | 32 | [49] |
| CXCL10 neutralization | CXCL10 antibodies induced by plasmid DNA vaccination; 100 µg im. by electroporation (50 µg each side) at 4 and 6 weeks | 58 | 26 | 30 | [155] |
| p38α-specific MAPK inhibitor | Indole-5-carboxamide (SD-169); 600 mg/kg in chow at 8–18 weeks | 60 | 10 | 18 | [156] |
| Regulatory T cells | CD4+CD25+CD62L+ cells from NOD.BDC2.5 mice expanded in vitro with antigen-pulsed DCs and IL-2; 5 × 104 cells at 13 weeks | 88 | 33 | 44 | [157] |
| CCL4 | Intradermal gene transfer using EBNA1/oriP-based vector; 1 µg weekly at 9–14 weeks | 78 | 30 | 35 | [158] |
| (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid | VGX-1027; 20 mg/kg ip. 6-times/week at 12–25 weeks | 81 | 31 | 25 | [159] |
| Cytopiloyne | 25 µg/kg ip. or im. 3-times/week beginning at 4 weeks | 67 | 0 | 30 | [160] |
| Apoptotic β-cells | 1 × 105 UVB-irradiated NIT-1 cells iv. weekly at 10–12 weeks | 100 | 62 | 30 | [161] |
| GM-CSF | 100 ng ip.; 3-times/week for 3 weeks and 2-times/week thereafter | 86 | 21 | 52 | [162] |
| Anti-CD20 | B cell-depleting anti-CD20 (MB20–11); 250 µg iv. at 5, 7 and 9 weeks | 100 | 36 | 40 | [57] |
| Microspheres carrying antisense oligonucleotides | Antisense oligonucleotides to CD40, CD80 and CD86; sc. proximal to pancreatic lymph nodes weekly at 5–13 weeks | 100 | 14 | 40 | [163] |
| Heparanase | 35 µg ip. 2-times/week at 6–14 weeks | 75 | 13 | 22 | [164] |
| TSLP | 500 ng sc. daily for 6 days at 3 weeks | 100 | 25 | 50 | [165] |
| TSLP-treated DCs | 5 × 106 iv. at 3 weeks | 87 | 25 | 45 | [165] |
| Inosine analog | INO-2002; 100 mg/kg by oral gavage daily at 5–30 weeks | 80 | 35 | 30 | [166] |
| GAD65-IgFc DNA (gene gun) | Gold particles coated with 1 µg DNA intradermally weekly at 10–13 weeks | 80 | 50 | 36 | [167] |
| Imatinib (Gleevec®) | 1.5 mg by oral gavage daily at 12–19 weeks | 71 | 25 | 30 | [168] |
| Anti-BLyS (BAFF) | B-cell-depleting anti-BLyS (10F4); 100 µg ip. at 4 weeks and again 5 days later; 15 µg biweekly at 8–25 weeks | 79 | 26 | 40 | [58] |
| Zymosan | Fungal cell wall component; 100 µg ip. 3-times/week every other week at 12–22 weeks | 90 | 40 | 42 | [50] |
| Galectin-1 | 100 µg ip. 3-times/week at 5–36 weeks | 78 | 0 | 37 | [169] |
| IL-25 (IL-17E) | 1 µg sc. daily for 25 days at 10 weeks | 90 | 30 | 26 | [74] |
| Anti-IL-17 | Neutralizing anti-IL-17 (50104); 100 µg ip. every other day for 12 days at 10 weeks | 90 | 40 | 24 | [74] |
| Mesenchymal stem cells (allogeneic) | 105 BALB.B cells ip. or iv. at 4 weeks | 100 | 59 | 36 | [170] |
| BAFF/APRIL blockade | 150 µg BCMA–Fc ip. 2-times/week at 9–15 weeks | 55 | 0 | 50 | [59] |
| Galectin-9 | 100 µg pCR3.1-I-Gal-9 plus 100 µg lipofectamine iv. weekly at 5–8 weeks | 86 | 15 | 40 | [171] |
| GAD65217–236/I-Ag7 dimers | 50 µg iv. for 3 days at 12 and 15 weeks | 100 | 20 | 35 | [172] |
| GAD65290–309/I-Ag7 dimers | 50 µg iv. for 3 days at 12 and 15 weeks | 100 | 10 | 35 | [172] |
| Anti-GITR ligand | Neutralizing anti-GITR ligand (YGL 386.2); 1 mg ip. weekly at 11–14 weeks | 100 | 33 | 32 | [75] |
| Immature DCs pulsed with InsB15–23 and InsB9–23 | Generated in GM-CSF, IL-10 and normal mouse serum; 106 ip. weekly at 5–12 weeks | 83 | 25 | 40 | [173] |
| Humanin | 2 mg/kg ip. daily beginning at 5 weeks | 60 | 30 | 20 | [174] |
| Newborn blood (allogeneic) | C57BL/6 whole blood (25–50 × 106 nucleated cells) iv. at 12 weeks | 80 | 30 | 28 | [175] |
| ECP-treated splenocytes | 2 × 105 cells iv. weekly at 8–12 weeks | 100 | 73 | 30 | [176] |
| Toxin-coupled IGRP206–214/H-2Kd tetramers | Saporin-conjugated tetramers; 34 pmoles iv. per injection; three injections, 6 days apart, beginning at 8 weeks | 100 | 50 | 30 | [177] |
Studies are listed in chronological order. All employed female NOD mice.
APRIL: A proliferation-inducing ligand; BAFF: B-cell-activating factor belonging to the TNF family; BCMA: B-cell maturation antigen; BLyS: B-lymphocyte stimulator; CCL: CC chemokine ligand; CXCL: CXC chemokine ligand; DC: Dendritic cell; EBNA: Epstein–Barr virus nuclear antigen; ECP: Extracorporeal photopheresis; GAD: Glutamic acid decarboxylase; G-CSF: Granulocyte colony-stimulating factor; GITR: Glucocorticoid-induced TNF receptor; GM-CSF: Granulocyte-macrophage colony-stimulating factor; IFA: Incomplete Freund’s adjuvant; IGRP: Islet-specific glucose-6-phosphatase catalytic subunit-related protein; im.: Intramuscularly; ip.: Intraperitoneally; iv.: Intravenously; MAPK: Mitogen-activated protein kinase; NOD: Nonobese diabetic; PSGL: P-selectin glycoprotein ligand; sc.: Subcutaneously; TSLP: Thymic stromal lymphopoietin; UVB: Ultraviolet B.