Table 2 Antigen specific immunotherapy in clinical trials

NCT01536431

Proinsulin (PI) peptide

i.d.

T1D

Phase I/II

Safe and well tolerated, reduction in the population of β-cell-specific effector memory CD8⁺ T cells, high fold change in Foxp3⁺CD25⁺ Tregs, and upregulation IL-10.⁶⁷²

Cardiff University

—

MBP (human) + PLP (Bovine)

oral

MS

—

Upregulation of specific TGF-β1 secreting T cells which population may be a distinct subset of T cells (Th3).^361,673

Brigham and Women’s Hospital and Harvard Medical School

ATX-MS-1467 (NCT01973491)

ATX-MS1 (MBP_30–44), ATX-MS7 (MBP_83–99), ATX-MS4 (MBP_131–145) and ATX-MS6 (MBP_140–154)

i.d./s.c.

MS

Phase II

Safety is unremarkable, reduction in T1 gadolinium-enhanced (GdE) lesions.^649,674

Merck KGaA, Darmstadt, Germany

ATX-MS-1467 (NCT01097668)

i.d./s.c.

MS

Phase I

Apitope Technology (Bristol) Ltd

(NCT00223613)

Insulin

intranasal

T1D

Phase III

Failed to prevent the development or delay of T1D for children with HLA susceptibility to diabetes⁶⁵³

University of Turku

—

Insulin

oral

T1D

—

Not showing significant effect to prevent the development or delay of T1D.⁶⁵⁴

University of Miami

—

Insulin

s.c./i.v.

T1D

—

Small doses are safe to persons at risk for diabetes but fail to prevent the development or delay of T1D for people at high risk for diabetes.⁶⁵⁵

Massachusetts Medical Society

MBP8298 (NCT00468611)

Synthetic peptide with a sequence corresponding to MBP_82–98.

i.v.

MS

Phase III

Safe and well tolerated, suppression of anti-MBP autoantibodies in CSF for most patients but not provide significant clinical treatment effect compared with the placebo.^650,651

BioMS Technology Corp

IMCY-0098 (NCT03272269)

Containing C20-A1 sequence (SLQPLALEGSLQKRG) and proprietary thioreductase motif

s.c.

T1D

Phase I

Safe and well tolerated, not significant decrease in C-peptide was detectable compared with baseline.⁶⁷⁵

Imcyse SA

NCT00837512

Insulin-Microneedle (depth less than 900 micrometers).

microneedle patch/s.c.

T1D

Phase II/III

Less pain than subcutaneous catheter; faster drug onset time than subcutaneous catheter.⁶⁷⁶

Emory University

NCT01684956

Insulin-Microneedle (MicronJet).

microneedle patch/s.c.

T1D

Phase II

—

Massachusetts General Hospital

—

Skin patch with a mixture of 3 myelin peptides, MBP_85–99, MOG_35–55, and PLP_139–155.

transdermal

MS

Phase II

Safe and well tolerated, activate Langerhans cells and induce unique granular DCs in LN, up-regulate Treg1 secreting IL-10, down-regulate IFN-γ and TGF-β and significant reduction of lesion by MRI.^477,677

Medical University of Lodz

KAN-101 (NCT04248855)

A liver-targeting glycosylation signature conjugated deaminated gliadin peptides

i.v.

CD

Phase I

Safe and well tolerated, drug is cleared from the systemic circulation in about 6 h.⁶⁷⁸

Anokion SA

ANK-700 (NCT04602390)

A liver-targeting glycosylation signature conjugated MS-related antigens.

i.v.

MS

Phase I

—

Anokion SA

Xemys

CD206-targeted liposomal-MBP_46–62, MBP_124–139 and MBP_147–170.

s.c.

MS

Phase I

Safe and well tolerated, significantly down-regulate MCP-1/CCL2, MIP-1β/CCL4, IL-7, and IL-2, up-regulate TNF-α and promote the normalization of cytokine.^679,680

Russian Academy of Sciences

NBI-5788 (NCT00079495)

APL for modification in the MBP_83–99 with a replacement Lys at position 91 with Ala.

s.c.

MS

Phase II

No development in disease for patients and no new MRI lesion was detected in 18 months of follow-up, cross-reaction is induced for native peptide but allergy symptoms happened in some patients.^396,400

Neurocrine Biosciences

CGP77116

APL of MBP_83–99, sequence modifications in the positions indicated by X (lower case, substitution by a D-amino acid): xXPVVHXFXNIVTPRTP.

s.c.

MS

Phase II

Poorly tolerated and safe, diseases developed and deteriorated in 3 patients and the clinical trial terminated.³⁹⁹

National Institute of Neurological Disorders and Stroke, Bethesda, USA

LY3209590

Combination of A-chain, B-chain for APL and IgG2 Fc domain.

s.c.

T1D

Phase II

Safe and well tolerated compared with Insulin Degludec, no significant change for HbA1c from baseline in patients.^681,682

Eli Lilly and Company

AG284

Solubilized DR2-MBP_84–102.

i.v.

MS

Phase I

Safe and well tolerated, the frequency of adverse events is similar to placebo, no significant treatment effect, and not establish tolerogenic T cells for MBP.⁶⁵²

University of California at San Francisco

NCT00411723

RTL1000(containing the outer two domains of HLA-DR2)-MOG_35-55.

i.v.

MS

Phase I

Dose of 60 mg or less is safe and well tolerated, significantly and effectively treating relapses MS development.⁶⁸³

Artielle ImmunoTherapeutics

(NCT00445913)

Autologous induced tolDCs in vitro.

i.d.

T1D

Phase I

Safe and well tolerated, no significant difference compared with baseline.⁵⁷⁸

University of Pittsburgh

(NCT01210664)

Autologous induced CD4⁺CD25^highCD127^-Tregs in vitro.

i.v.

T1D

Phase I

Safe and well tolerated, the transferred Tregs was long-lived in vivo for patients and increase Treg suppressive activity in vitro.^585,586

University of California, San Francisco

(NCT01352858)

Autologous induced tolDCs by autologous synovial fluid.

arthroscopical injection

RA

Phase I

Safe and well tolerated but no significant clinical treatment effects were detectable.⁶⁸⁴

Newcastle University

(ISRCTN06128462)

Autologous induced Tregs in vitro.

i.v.

T1D

Phase I

Safe and well tolerated, the transform from naïve CD62L⁺CD45RA⁺ to memory CD62L⁺CD45RA^- Tregs and decrease in serum levels of proinflammatory cytokines.⁶⁸⁵

Medical University of Gdansk

—

Autologous CD4⁺ CD25^high CD127^- Tregs.

i.v.

T1D

Phase I

Safe and well tolerated, significantly high plasma C-peptide levels in treated group.⁶⁸⁶

Medical University of Gdansk

—

TolDCs pulsed with proinsulin peptideC19-A3.

i.d.

T1D

Phase I

Safe and well tolerated, β-cell function and diabetic condition keep a stable level in 6 months of monitoring and all patients with stable HbA1c values.⁶⁸⁷

Leiden University Medical Center

—

RBCs coupled with MBP_13–32, MBP_83–99, MBP_111–129, MBP_146–170, MOG_1–20, MOG_35–55, and PLP_139–154.

i.v.

MS

Phase I

Safe and well tolerated, reduction in specific T cell for myelin peptides in high dose group, induce generation of IL-10, Tr1 and Tregs.⁶⁸⁸

University of Zurich

NCT02283671

TolDCs coupled with MBP_13–32, MBP_83–99, MBP_111–129, MBP_146–170, MOG_1–20, MOG_35–55, PLP_139–154 and AQP4_63–76.

i.v.

MS/NMOSD

Phase I

Safe and well tolerated, induce the generation of Tr1, specific T cells, and PBMCs secreting IL-10 and decrease memory CD8⁺ T cells and NK cells.⁵⁶⁰

Sara Varea

—

PBMCs coupled with MBP_13–32, MBP_83–99, MBP_111–129, MBP_146–170, MOG_1–20, MOG_35–55, and PLP_139–154.

i.v.

MS

Phase I

Safe and well tolerated, decrease antigen-specific T cells (higher dose) and stabilize the frequency for Tr1, Tregs, and TH2 cells.⁵⁷⁴

Center for Molecular Neurobiology, 20251 Hamburg, Germany

NCT05451212

CAAR-T targeting MuSK.

i.v.

MG

Phase I

—

Cabaletta Bio

BHT-3009 (NCT00382629)

DNA vaccine encoding full-length human MBP.

i.m.

MS

Phase II

Lower 0.5 mg BHT-3009 was safe and well tolerated, reduction in lesion by MRI, autoreactive T cells activity, and anti-myelin autoantibodies in CSF.⁶⁰⁵

Bayhill Therapeutics

BHT-3009 (NCT00103974)

DNA vaccine encoding full-length human MBP.

i.m.

MS

Phase I

Not showing significant effect to prevent the development or delay of T1D.⁶⁰⁶

Bayhill Therapeutics

BHT-3021 (NCT00453375)

DNA vaccine encoding the whole proinsulin molecule.

i.m.

T1D

Phase I

Safe and well tolerated, 1 mg of BHT-3021 is the most effective, good control of HgbA1c and reduction in antigen-specific CD8⁺ T cells.⁶⁰²

Bayhill Therapeutics