Partnership Aims at Cell Therapy Targeting Epstein-Barr Virus in MS

NexImmune, NINDS team to develop way to selectively kill EBV-infected cells

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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NexImmune is working with the National Institute of Neurological Disorders and Stroke (NINDS) to develop cell therapies for people with immunological disorders associated with certain viral infections, namely the Epstein-Barr virus (EBV) and human T-cell leukemia virus type 1 (HTLV-1).

A history of infection with EBV — mostly known for causing infectious mononucleosis, or mono — is currently the strongest risk factor for multiple sclerosis (MS).

After infection, the virus remains in the body in a dormant form inside B-cells — a type of immune cell implicated in MS — and studies suggest that these infected cells may be involved in initiating the autoimmune attack that drives neurodegeneration in multiple sclerosis.

In turn, HTLV-1 infection can cause a rare inflammatory disorder of the spinal cord called HTLV-1 associated myelopathy.

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“Compelling evidence exists that several autoimmune diseases are mediated by virally-infected cells. Current therapeutic approaches in these diseases broadly target cell populations that may or may not be expressly involved in the disease,” Kristi Jones, NexImmune’s CEO, said in a company press release.

The company’s cell-based approach “has the potential to selectively target and eliminate EBV-infected B cells … or HTLV-1-infected cells … which may offer a unique benefit over current approaches,” Jones added.

Looking into Epstein-Barr virus as selective target for MS

NexImmune and NINDS scientists will focus on enriching and expanding T-cell populations that are able to kill cells infected with the respective viruses.

T-cells are immune cells equipped with a cell-surface receptor called a T-cell receptor (TCR), which is able to bind to a specific molecular target, called an antigen — for example, a piece of a virus. When the TCR binds to its antigen, it triggers the T-cell to launch an inflammatory attack to destroy the threat.

Within the body, T-cells are mainly activated by antigen-presenting cells (APCs). As their name implies, APCs can take up antigens and present them to T-cells, helping to activate the T-cell.

NexImmune’s therapeutic approach is based on its nanotechonology platform, called Artificial Immune Modulation or AIM. The platform allows the creation of nanoparticles that function as artificial APCs, intending to promote a T-cell-driven inflammatory attack against a specific antigen.

“We will be working with the NINDS to evaluate EBV and HTLV-1 as therapeutic targets in the [mechanisms behind] neurological immune diseases,” Jones said. “This important collaboration will enable us to leverage the AIM platform to develop potentially innovative antigen-specific therapies for these patients.”

Notably, this approach — called AIM adoptive cellular therapy and being evaluated in clinical trials for certain blood cancers — involves collecting a patient’s own T-cells and expanding them in the lab in the presence of antigen-specific AIM nanoparticles.

This is expected to create a pool of T-cells against a particular antigen, like that of a virus. The T-cells are then returned to the patient via an infusion.

“There is a clear causal relationship between HLTV-1 infection and HTLV-1 Associated Myelopathy and a potential relationship between EBV infection and MS,” said David Hafler, MD, chair of the neurology department at the Yale School of Medicine and a member of NexImmune’s scientific advisory board.

“This work will help advance our understanding of the role immune responses to viral infection play in different neuroimmunological diseases,” he added.

NINDS is a division of the U.S. National Institutes of Health.

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