Immune Tolerance in Autoimmune Disease

Autoimmune diseases occur when the immune system mistakenly flags certain cells in the body as foreign invaders. The resulting attack can cause irreparable damage to critical organs and tissues. For example, in multiple sclerosis, it’s the myelin coating that insulates nerve cells; in lupus, it can be any number of organs or systems that are damaged. Currently, many of the primary methods to treat patients with autoimmune disease utilize immune suppressors, which help reduce the inflammatory attack on tissues but can put patients at higher risk for developing infections.

Immune tolerance therapies are designed to stop, or even prevent, the autoimmune disease while leaving the body's disease-fighting abilities intact. These tolerance therapies essentially reprogram the immune system, so that a short course of treatment will have long-lasting, perhaps lifelong effects. While immune tolerance therapies are mainly experimental, the Immune Tolerance Network (ITN) believes that targeted reprogramming of the immune system holds a great deal of promise to effectively treat autoimmune diseases with fewer side effects than current drugs.

Research Focus - Autoimmune Disease

The clinical heterogeneity of the more than 80 autoimmune diseases presents a significant challenge with respect to the development of therapies designed to re-establish self-tolerance. The ITN’s approach to tolerance in autoimmune diseases attempts to address these challenges through a coordinated program of clinical studies aimed at establishing proof-of-principle either in diseases where a self-antigen has been identified, the target organ is accessible for further study or the disease pathogenesis has been relatively well established.

Given the complex nature of these diseases, and following the approaches being developed in the transplant and allergy portfolios, the ITN builds on results from ongoing trials by developing combination approaches affecting humoral and cellular, as well as adaptive and innate, immune responses. This includes combinations that ablate or anergize effector responses, deviate induced responses and boost regulatory responses. Because combination therapy trials can be logistically and scientifically challenging, the ITN has adopted the use of smaller, mechanistically-based studies as a first step in evaluating promising combinations and establishing a mechanistic plan that will inform on the pathways of tolerance.

Principal Investigator:

Doruk Erkan | Hospital for Special Surgery | New York, NY

Jason Knight | University of Michigan | Ann Arbor, MI

A study about the safety of daratumumab in patients with antiphospholipid syndrome (APS), and its effectiveness at reducing the antiphospholipid antibodies that cause APS.

Category: 

Autoimmune Disease

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Specific Category: 

Primary Antiphospholipid Syndrome

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Status: 

Enrollment

Principal Investigator:

E. William St. Clair | Immune Tolerance Network | Durham, NC

The goal of CONTROL-RA is to see how the experimental study drug, VIB4920, affects control of rheumatoid arthritis (RA).

Category: 

Autoimmune Disease

|

Specific Category: 

Autoimmune Diseases

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Status: 

On Hold

Principal Investigator:

Maria Dall'era | University of California San Francisco | San Francisco, CA

Betty Diamond | The Feinstein Institute for Medical Research | Manhasset, NY

David Wofsy | University of California San Francisco | San Francisco, CA

The goal of the VIBRANT trial is to determine if treating lupus nephritis with VIB4920 in addition to standard therapy is more effective than treating lupus nephritis with standard therapy alone.

Category: 

Autoimmune Disease

|

Specific Category: 

Lupus Nephritis

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Status: 

Enrollment

Principal Investigator:

Brett King | Yale School of Medicine | Middlebury, CT

The REVEAL study will investigate whether the experimental study medication, AMG714, can bring back normal color to the skin in vitiligo.

Category: 

Autoimmune Disease

|

Specific Category: 

Vitiligo

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Status: 

Follow-up

Principal Investigator:

Patrick Nachman | University of Minnesota | Minneapolis, MN

REBOOT will test whether a combination of, belimumab and rituximab, is safe and if this combination is more effective at blocking the immune attack on the kidney of patients with Primary Membranous Neuropathy (MN).

Category: 

Autoimmune Disease

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Specific Category: 

Autoimmune Diseases

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Status: 

Enrollment

Principal Investigator:

Jeffrey Cohen | Cleveland Clinic | Cleveland, OH

Paolo Muraro | Imperial College London | London, England

George Georges | Fred Hutchinson Cancer Research Center | Chicago, IL

BEAT-MS is a clinical trial comparing chemotherapy followed by autologous hematopoietic stem cell transplant (AHSCT) – a type of bone marrow transplantation – to the most effective medicines regularly used to treat relapsing MS.

Category: 

Autoimmune Disease

|

Specific Category: 

Multiple Sclerosis

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Status: 

Enrollment

Principal Investigator:

Dinesh Khanna | University of Michigan | Ann Arbor, MI

David Fox | University of Michigan | Ann Arbor, MI

BRAVOS is a clinical trial evaluating Brentuximab Vendotin treatment for Diffuse Cutaneous Systemic Sclerosis.

Category: 

Autoimmune Disease

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Specific Category: 

Scleroderma

|

Status: 

Analysis

Principal Investigator:

James Krueger | The Rockefeller University | New York, NY

PAUSE is a clinical trial testing the effectiveness of ustekinumab (STELARA ®) followed by an investigational drug, abatacept, for the treatment of psoriasis. The main goal of the study is to determine the efficacy of abatacept to induce prolonged remission.

Category: 

Autoimmune Disease

|

Specific Category: 

Psoriasis Vulgaris

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Status: 

Complete

Principal Investigator:

Cynthia Aranow | North Shore Hospital | Manhasset, NY

Maria Dall'era | University of California San Francisco | San Francisco, CA

David Wofsy | University of California San Francisco | San Francisco, CA

The objective of the CALIBRATE study is to determine if treating lupus nephritis with a combination of rituximab (Rituxan®) and cyclophosphamide (Cytoxan®), or a combination of rituximab and cyclophosphamide followed by treatment with belimumab (Benlysta®) is safe and if this drug combination can block the immune system attacks on the kidney.

Category: 

Autoimmune Disease

|

Specific Category: 

Lupus

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Status: 

Complete

Principal Investigator:

Lloyd Mayer | Mount Sinai Hospital | New York, NY

The purpose of this study is to determine whether Immucothel, a Keyhole Lymphocyte Antigen (KLH) product, can trigger an immune response when ingested orally and create "oral tolerance" to KLH. If not, Immucothel will be tested with another agent to enhance the immune response.

Category: 

Autoimmune Disease

|

Specific Category: 

Healthy Controls

|

Status: 

Complete

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