Targeting EBV as a therapy: Allogeneic EBV T-cell therapy

[frodo]

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.