Table 3.
Antigen-specific approaches pursued by biotech companies and academic laboratories.
| Form of delivery | Approach | Disease | Peptide used | Route | Company/University | Stage | Link or Reference |
|---|---|---|---|---|---|---|---|
| Free peptides | Mimotope with stronger MHCII-binding | T1D | Insulin9-23 mimotope | SC | Helmholtz Zentrum München | Pre-clinical | Refs.67,68 |
| Apitopes®: tolerogenic peptides | MS | Four myelin-derived peptides | ID | Worg Pharmaceuticals | Phase 2 | http://www.worgpharma.com | |
| Imotopes®: thioredoxin-Ag to augment pMHC-TCR interactions | T1D, MS | PPI-derived peptide, MOG-derived peptide | SC | Imcyse/University of Leuven | Phase 2 | https://www.imcyse.com, Ref.69 | |
| Multiple insulin peptides | T1D | PPIC13-C32, PPIC19-A3, PPIC22-A5, IA2718-36, IA2752-75, IA2855-67 | ID | King’s College London | Phase 3 | Ref.70 | |
| Conjugated peptides | Galactose or N-acetyl-galactosamine-terminating Ags | T1D, MS | p31 mimotope, myelin-derived peptides | IV | Anokion | IND, Phase 1 | https://anokion.com |
| Soluble Ag Arrays (SAgAs) | T1D | p79 mimotope, 2.5HIP | SC | University of Kansas/Columbia University | Pre-clinical | Ref.71 | |
| Abs conjugated peptides targeting DCs (aDEC, aDCIR) | T1D | p31 mimotope | IP | NIH | Pre-clinical | Ref.72 | |
| Peptide carrying-NPs | PLGA co-delivery of Ag and rapamycin | PBC | PDH-E2-derived peptide | IV | Selecta Biosciences | Pre-clinical | https://selectabio.com |
| Liposome or gold NPs co-delivery of Ag and AhR ligand | T1D, MS | PPI-derived peptides, MOG35-55 | SC, IV | Antolrx/Pfizer | Pre-clinical | https://antolrx.com, Ref.73 | |
| Synthetic HDL to deliver Ag | T1D | NOD Ag | SC | Evoq Therapeutics | Pre-clinical | https://www.evoqtherapeutics.com | |
| pSER liposomes taken up as apoptotic cells | T1D | Ins90-110 and Ins25-54 | IP | Ahead Therapeutics/Universitat Autonoma de Barcelona | Pre-clinical | https://www.aheadtherapeutics.com, Ref.74 | |
| PLG NPs uptake by phagocytes | T1D | 2.5HIP | IV | University of Colorado/Northwestern University/Cour Pharmaceuticals | Pre-clinical | https://courpharma.com, Ref.75 | |
| Super paramagnetic iron oxide NPs (Spions®) | PV | Desmoglein 3-derived peptides | IV | Topas Therapeutics | Phase 1 | https://topas-therapeutics.com | |
| NPs made of polymerized ursodeoxycholic acid | T1D | INS (protein, adaptable to peptides) | Oral | Toralgen/Yale University | Pre-clinical | https://toralgen.com, Ref.76 | |
| mRNA carrying-NPs | Liposome with mRNA-encoding Ags | MS | MOG35-55 | IV | BioNTech/University of Mainz | Pre-clinical | Ref.77 |
| DNA vectors | Plasmid encoding Ag and targeting lysosomal compartment | T1D | p31 mimotope | IV | University of Barcelona | Pre-clinical | Ref.78 |
| Plasmid encoding Ag, TGF-β1, IL-10, IL-2 | T1D | PI (protein, adaptable to peptides) | SC | Novo Nordisk | Phase 1 | Ref.49 | |
| Plasmid encoding multiple Ags (Endotope) | T1D | InsB9-23 p8E and p8 G mimotope, p79 mimotope, InsB9–23, GAD65286-300, GAD65524-543, InsB15–23, IGRP206-214 | IM, ID | Columbia University | Pre-clinical | Ref.53 | |
| Modified bacteria | Lactococcus lactis expressing IL-10, Ag | T1D | PI (protein, adaptable to peptides), GAD375-575 | Oral | Precigen Actobio/University of Leuven | Phase 1/2 | https://precigen.com, Refs.79,80 |
| Bacterium-like particles | T1D | IA-2ic (protein, adaptable to peptides) | Oral | Wuhan University | Pre-clinical | Ref.81 | |
| Modified erythrocytes | RBCs (or PBMCs) coupled with Ag | MS | Seven myelin-derived peptides | IV | Cellerys/Novartis/University of Zurich | Phase 2 | https://www.cellerys.com |
| RBCs loaded with Ag | T1D | p31 mimotope | IV | SQZ Biotech | Pre-clinical | https://sqzbiotech.com | |
| RBCs transduced with Ag | T1D | p31 mimotope | IV | Rubius Therapeutics | Pre-clinical | https://www.rubiustx.com | |
| Soluble pMHC complexes | Dimeric MHC II-peptide chimera | T1D | GAD65217-230 | IV | Mount Sinai School of Medicine | Pre-clinical | Ref.82 |
| APCs/APNPs | Tolerogenic DCs | T1D | PIC19-A3 | ID | Leiden University, City of Hope Medical Center | Phase 2 | Ref.83 |
| Iron oxide NPs with large density arrays of pMHC (Navacims®) | T1D, MS, PBC | GAD65555-567, PI76–90, IGRP13-25, MOG38-49, PDH-E2166-181 | IV, SC | Parvus Therapeutics/University of Calgary | Pre-clinical | https://parvustx.com, Ref.84 |
Ag, Antigen; NP, nanoparticle; APCs, antigen-presenting cells; APNP, antigen-presenting nanoparticles; aDEC, anti-DEC205; aDCIR, anti-DCIR2; PLGA, poly(lactic-co-glycolic acid); pSER, phosphatidyl-serine; RBCs, red blood cells; DCs, dendritic cells; T1D, Type 1 diabetes; MS, multiple sclerosis; PBC, primary biliary cirrhosis; PV, pemphigus vulgaris; MOG, myelin oligodendrocyte glycoprotein; PI, proinsulin; PPI, preproinsulin; NOD, non-obese diabetic; IA, insulinoma-associated; HIP, hybrid insulin peptide; INS, insulin; PDH-E2, pyruvate dehydrogenase-E2; GAD, glutamic acid decarboxylase; IGRP, islet-specific glucose-6-phosphatase catalytic subunit-related protein; SC, subcutaneous; ID, intradermal, IV, intravenous; IP, intraperitoneal.