EBV Autologous T-Cell Therapy: Long Term Results

[NHE]

Sustained Clinical Improvement in a Subset of Patients With Progressive Multiple Sclerosis Treated With Epstein-Barr Virus-Specific T Cell Therapy
Front Neurol. 2021 Mar 15;12:652811.

Background: Increasing evidence indicates a role for Epstein-Barr virus (EBV) in the pathogenesis of multiple sclerosis (MS). EBV-infected autoreactive B cells might accumulate in the central nervous system because of defective cytotoxic CD8+ T cell immunity. We have previously reported results of a phase I clinical trial of autologous EBV-specific T cell therapy in MS 6 months after treatment.

Objective: To investigate longer-term outcomes in MS patients who received autologous EBV-specific T cell therapy. Methods: We assessed participants 2 and 3 years after completion of T cell therapy.

Results: We collected data from all 10 treated participants at year 2 and from 9 participants at year 3. No serious treatment-related adverse events were observed. Four participants had at least some sustained clinical improvement at year 2, including reduced fatigue in three participants, and reduced Expanded Disability Status Scale score in two participants. Three participants experienced a sustained improvement in at least some symptoms at year 3. More sustained improvement was associated with higher EBV-specific CD8+ T cell reactivity in the administered T cell product.

Conclusion: Autologous EBV-specific T cell therapy is well-tolerated, and some degree of clinical improvement can be sustained for up to 3 years after treatment.

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[frodo]

Updated March 2023: I think this refers to the same treatment

Adoptive T-cell therapy targeting Epstein–Barr virus as a treatment for multiple sclerosis

https://onlinelibrary.wiley.com/doi/ful ... /cti2.1444

Abstract

Emergence of a definitive link between Epstein–Barr virus (EBV) and multiple sclerosis has provided an impetus to develop immune-based therapies to target EBV-infected B cells.

Initial studies with autologous EBV-specific T-cell therapy demonstrated that this therapy is safe with minimal side effects and more importantly multiple patients showed both symptomatic and objective neurological improvements including improved quality of life, reduction of fatigue and reduced intrathecal IgG production.

These observations have been successfully extended to an ‘off-the-shelf’ allogeneic EBV-specific T-cell therapy manufactured using peripheral blood lymphocytes of healthy seropositive individuals. This adoptive immunotherapy has also been shown to be safe with encouraging clinical responses.

Allogeneic EBV T-cell therapy overcomes some of the limitations of autologous therapy and can be rapidly delivered to patients with improved therapeutic potential.


Conclusions

While the contribution of brain-resident EBV-transformed B cells to the pathogenesis of MS remains to be fully elucidated, our thorough understanding of the latent lifecycle of EBV, and the immune mechanisms that control persistent infection, has enabled the translation of an EBV-specific cellular therapy initially developed to treat EBV-associated malignancies into a promising treatment for patients with progressive MS.

This adoptive immunotherapy is specifically designed to target EBV-infected autoreactive B cells which may be contributing to the pathogenesis of MS.

Clinical studies using both autologous and allogeneic T-cell therapies have shown that this therapeutic strategy is safe with minimal side effects and clinical benefit observed in some patients is sustained for long-term.

In future, this T-cell therapy may be complemented with a therapeutic vaccine which specifically enhances T-cell immunity to EBV latent antigens, which are expressed in EBV-infected B cells.

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