Table 4.
Cell-based vaccination.
| Cells | Inductive Agent/Peptide | Vaccination Type | Admin. Route | Admin. Dose | Animal Model | Vaccination Outcome |
|---|---|---|---|---|---|---|
| Tolerogenic Dendritic cells (tolDCs) | ||||||
| BMDCs from C57BL/6 mice [161] | Atorvastatin/MOG35–55 | Preclinical/Therapeutic: days five and 13 p.i. | i.p. | 1 × 106 cells per injection | Female C57BL/6 mice (8–10 weeks old) with EAE induced with MOG35–55 | MOG35–55—specific tolDCs successfully ameliorated clinical Symptoms in mice with EAE. |
| BMDCs [162] | mytomycin C/MOG196–204 | Admin. of MOG196-pulsed Kb−/−Db−/− DCs to C57BL/6 (B6) mice one week b.i. and one p.i. Admin. of MOG196-pulsed B6 DCs to C57BL/6 mice three days b.i. and two and seven days p.i. |
s.c. | 1 × 106 cells per injection | Female C57BL/6 (B6) (8–10 weeks old) with EAE induced with MOG35–55 | Administration of MOG196-pulsed Kb−/−Db−/− DCs or MOG196-pulsed DCs ameliorated EAE in mice. |
| Murine BMDCs [154] | 1α, 25-dihydroxy-vitamin D3/MOG-encoding mRNA or MOG35–55 | Therapeutic: 13, 17, and 21 days p.i. | i.v. | 1 × 106 cells per injection | Female C57BL/6JOlaHsd mice (8–10 weeks old) with EAE induced with MOG35–55 | Vaccination with tolDCs electroporated with MOG-encoding mRNA or MOG35–55 stabilized the clinical signs of the disease already from the first injection. MRI examination of hyperintense spots present along the spinal cord of mice was found to be in line with the clinical score (Figure 9). |
| BMDCs [163] | CD40-specific and p19-specific shRNA encoding lentiviral vectors/pyromycin/MOG35–55 | Preclinical/Thereapeutic: 3, 5, and 7 days p.i. | i.v. | 2 × 106 cells per injection | C57BL/6 mice with EAE induced with MOG35–55 | Administration of MOG35–55-pulsed and lentiviral transduced BMDCs led to significant decrease in the clinical symptoms of EAE in mice. The highest decrease in the clinical scores was observed with the administration of co-transduced BMDCs (BoLV-DCs). |
| BMDCs [164] | Vitamin D3/MOG40–55 | Preclinical/Therapeutic: two and five days p.i., or five and nine days p.i. or 15, 19, 23, and 33 days p.i. | i.v. | 2 or 4 × 106 cells | Female C57BL/6J mice (8–10 weeks old) with EAE induced with MOG40–55 | MOG40–55—specific TolDCs were found to succeed in reducing EAE incidence and ameliorating its clinical signs. |
| BMDCs [165] | Vitamin D3/MOG40–55/cryopreserved | i.v. | 2 or 4 × 106 cells | Female C57BL/6J mice (8–10 weeks old) with EAE induced with MOG40–55 | It was shown that MOG40–55—specific TolDCs maintain their tolerogenic properties and can efficiently ameliorate the clinical symptoms of EAE. | |
| Murine BMDCs [166] | Tofacitinib/MOG35–55 | Therapeutic: 7, 11, and 15 days p.i. | i.v. | Twelve-week Female C57BL/6 mice (12 weeks old) with EAE induced with MOG35–55 | MOG35–55—specific TolDCs efficiently dampened EAE severity and progression. | |
| BMDCs [167] | 1,25-dihydroxyvitamin D3/MOG35–55 | Therapeutic: 10, 13, and 16 days p.i. | i.v. | Female C57BL/6 mice (6–8 weeks old) with EAE induced with MOG35–55 | Vitamin D3 treated MOG35–55—specific. TolDCs succeeded in postponing the disease onset and reducing its clinical scores. | |
| DCs [168] | Estriol (E3)/MOG35–55 | Prophylactic: one day b.i. | i.v. | 8–10 × 106 cells per mouse | Female C57BL/6 (H-2b) mice (4–6 weeks old) with EAE induced with MOG35–55 | Mice vaccinated with E3 MOG35–55—specific TolDCs exhibited a reduced cumulative clinical score and EAE severity. They also avoided relapses and development of chronic disease. |
| BMDCs matured with TNF-α [169] | /MOG35–55 | Prophylactic: 7, 5, 3, and 1 days b.i. Preclinical: one day p.i. |
i.v. | 2–2.5 × 106 cells per injection Rat anti–mouse IL-10R mAb: 0.5 mg equivalents per mouse | C57Bl/6 mice with EAE induced with MOG35–55 | Vaccination with MOG35–55—specific TNF/DCs improved the clinical disease score. Pulsing of TNF-α/DCs with an unrelated peptide did not succeed in preventing the disease. |
| DCs [170] | /in vivo pulsing in Lewis rats with EAE induced with MBP68–86 | Prophylactic: four weeks b.i. | s.c. | 1 × 106 cells per rat | Male Lewis rats with EAE induced with MBP68–86 | Injection of EAE DCs to rats resulted in induction of immune tolerance against the disease as demonstrated by delayed onset and marked decrease of the mean clinical score. |
| T cell-based vaccination | ||||||
| Ob2F3 Tregs [171] | Retrovirally transduced pre-stimulated naïve CD4+ Tcells from peripheral blood mononuclear cells (PBMCs) of healthy donors using Ob2F3. | Preclinical/Therapeutic: seven days p.i. | i.v. | 2 × 106 cells | Male and female HLA-DR15 transgenic mice (4.5–7.5 months old) with EAE induced with MOG35–55 | Ob2F3 Tregs were shown to significantly ameliorate MOG35–55 induced EAE via bystander suppression. |
| MBP-specific T-cell lines (e.g., B12 and B12-GFP) [157] | Prophylactic: admin. three times at weekly intervals, with the last injection 10 or seven days b.i. | s.c. | 1 × 107 activated and irradiated T cells | Female Lewis rats (6–8 weeks old) with EAE induced via i.v. injection of antigen stimulated T cells. | Vaccination with MBP-specific T cell lines inhibited the development of EAE clinical symptoms. | |
| Hematopoietic stem cells (HSCs) | ||||||
| DC-MOG vector-transduced BM-HSC [172] | Ex vivo modification of HSCs with SIN lentivirus vectors which transcriptionally target the expression of myelin peptides to DCs. | Prophylactic: Lethally Irradiated (10.5 Gy) mice were transplanted with DC-MOG transduced BM-HSCs eight weeks b.i. BM chimeras received neomycin treatment for three weeks post transplantation. | i.v. | 1–3 × 106 cells per mouse | C57BL/6 mice with EAE induced with MOG peptide. | The transplantation of DC-MOG vector-transduced BM-HSC was found to completely protect mice from developing EAE even in cases of transplantation 6 months b.i. In agreement with the clinical observations, no histological signs of the disease such as demyelination, damage of axons, etc. could be detected in the tolerized mice. |
| Bone marrow cells (BMC) | ||||||
| BMCs expressing MOG40–55 [173] | liMOG | Prophylactic: mice were transplanted with BMCs transduced with liMOG 21 days b.i. Therapeutic: mice were transplanted with transduced BMCs 15–17 days p.i. |
i.v. | 0.7–1.6 × 106 cells per mouse | Female C57BL/6J mice (5–10 weeks old) with EAE induced with MOG40–55 | Transplantation of BMCs expressing MOG40–55 was shown to protect mice from developing EAE and reduce the disease severity in mice with established EAE. |
| Myeloid-derived suppressor cells (MDSCs) | ||||||
| MDSCs isolated via positive selection from BMCs expressing MOG40–55 [174] | liMOG | Prophylactic: mice were transplanted with MDSCs transduced with liMOG seven days b.i. Therapeutic: mice were transplanted with transduced MDSCs 13–14 days p.i. |
i.v. | 0.5–1 × 106 cells per mouse | Female C57BL6/J mice (6–8 weeks old) with EAE induced with MOG40–55 | MOG40–55 -expressing MDSCs were found to exhibit both preventive and therapeutic effects in EAE induced with MOG40–55 |
| Antigen-cell conjugates | ||||||
| Ag-SP [158] | Chemically treated Ag-coupled SPs | Administration on day −7 b.i. or at peak of disease in actively induced EAE, or two days p.i. | i.v. | 50 × 106 Ag-SPs per mouse | Wild-type C57BL/6 (I-Ab), B10.S (I-As), and BALB/c (I-Ad) female mice (5–6 weeks old) with EAE induced with myelin peptide or via adoptive transfer. | It was revealed that syngeneic or allogeneic Ag-SPs can effectively protect mice against ongoing clinical EAE. |
| Ag-SP [159] | Chemically treated Ag-coupled SPs | Prophylactic: at indicated time points b.i. | i.v. | 50 × 106 Ag-SPs or 15–20 μg Ag per mouse | SJL and C57BL/6 mice with EAE induced with myelin peptide or via adoptive transfer. | i.v. infusion of peptide antigens coupled to syngeneic splenic leukocytes (Ag-SP) was found to efficiently induce antigen-specific T cell tolerance. |
| Ag-RBC [160] | Genetically engineerd Kell-LPETGG RBCs, coupled with MOG 35–55 through enzymatic surface modification with sortase transpeptidase. | Prophylactic: transfusion seven days b.i. Preclinical: transfusion five days p.i. Therapeutic: Transfusion on the day of EAE onset |
i.v. | 200 μL RBC-MOG35–55 | C57BL/6J (CD45.2+), B6.SJL-Ptprc (CD45.1+), BALB/c Female C57BL/6 mice (10–12 weeks old) with EAE induced with MOG35–55 | The transfusion of RBC-MOG35–55 was shown to significantly improve the clinical signs of EAE in mice. |
BMDCs: Bone marrow-derived dendritic cells; p.i.: post immunization; i.p.: intraperitoneal; EAE: experimental allergicencephalomyelitis; tolDCs: tolerogenic dendritic cells; s.c.: subcutaneous; b.i.: before immunization; i.v.: intravenous; MBP: myelin basic protein; Tregs: regulatory T cells; Ob2F3: recombinant T-cell receptor (TCR) isolated from a MBP specific Tcell clone of a multiple sclerosis patient; HSCs: hematopoietic stem cells; SIN: selfinactivating; SP: splenocytes; RBCs: red blood cells; liMOG: vector encoding the murine invariant chain (Ii) containing MOG40–55 and enhanced green fluorescent protein (EGFP).