Specialized Antibodies Can ‘Disarm’ NMOSD-causing Autoantibody

New therapy neutralizes self-reactive antibodies in both in vitro, in vivo conditions

Patricia Valerio, PhD avatar

by Patricia Valerio, PhD |

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SAB Biotherapeutics’ DiversitAb platform has generated specialized antibodies against multiple regions of an abnormal self-reactive antibody, or autoantibody, associated with neuromyelitis optica spectrum disorder (NMOSD).

The new antibody-based therapy was found to effectively bind to the NMOSD-causing autoantibody and neutralize it in both in vitro (in lab dishes) and in vivo (inside a living organism) conditions.

The project is part of a collaboration with CSL to help treat autoimmune diseases such as NMOSD.

“As the scientific community begins to better understand the varying and complex nature of autoimmune disorders, it is important we research and develop therapies to provide robust efficacy against multiple autoantibodies driving an autoimmune disease,” said Alexandra Kropotova, MD, SAB’s chief medical officer, in a company press release. “Our DiversitAb platform has proven its ability to create an ‘antidote’ antibody treatment that can ‘disarm’ those harmful autoantibodies without a broad immunosuppressive effect — having implications across a wide variety of autoimmune diseases.”

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Age at Onset of NMOSD Influences Disease Presentation, Prognosis

Antibodies are proteins produced by the immune system to fight infections and cancer. When they fail to properly recognize the body’s healthy cells or molecules, they are called autoantibodies and are associated with a number of autoimmune diseases, such as NMOSD.

A protein on the surface of neuron-supporting brain cells called AQP4 is the most common target of disease-causing autoantibodies in NMOSD. Other autoantibodies may also be involved in some cases, however.

Together with CSL, SAB has been working on its DiversitAb platform to produce functional and fully-human anti-idiotypic polyclonal antibodies to target and disarm the autoantibodies associated with autoimmune diseases.

An anti-idiotypic antibody binds to an idiotope of another antibody. The idiotope is the antibody’s variable part that binds to a specific antigen, or part of a molecule that can be recognized by the immune system.

Polyclonal antibodies are produced using different immune cells. Since each immune cell recognizes only a specific portion of a given molecule, a treatment based on polyclonal antibodies means several parts of that molecule will be targeted, not just one.

The platform generates the specialized, yet broadly neutralizing polyclonal antibodies, without human donors, unlike standard production methods. It’s instead based on so-called transchromosomic cows, which are genetically modified to carry human genes.

Now, in vitro and in vivo results have shown the DiversitAb platform could use a NMOSD-associated autoantibody to develop an effective polyclonal antibody-based treatment.

“The promising results from this platform capabilities project are an important step in developing a scalable, effective and fully-human anti-idiotype therapeutic for people living with autoimmune disorders that are in need of treatment options,” said Eddie Sullivan, SAB’s co-founder, president, and CEO. “The unique capabilities of our transchromosomic cows and DiversitA platform continue to prove the power of polyclonals to address complex and very difficult to treat autoimmune diseases.”