The Promise and Challenges of Cell Therapy for Psoriasis

S.M. Lwin; J.A. Snowden; C.E.M. Griffiths

Disclosures

The British Journal of Dermatology. 2021;185(5):887-898. 

In This Article

Abstract and Introduction

Abstract

The management of moderate-to-severe psoriasis has been transformed by the introduction of biological therapies. These medicines, particularly those targeting interleukin (IL)-17 and IL-23p19, can offer clear or nearly clear skin for the majority of patients with psoriasis, with good long-term drug survival. However, as currently used, none of these therapies is curative and disconcertingly there is a small but increasing number of patients with severe psoriasis who have failed all currently available therapeutic modalities. A similar scenario has occurred in other immune-mediated inflammatory diseases (IMIDs) where treatment options are limited in severely affected patients. In these cases, cell therapy, including haematopoietic stem cell transplantation (HSCT) and mesenchymal stromal cells (MSC), has been utilized. This review discusses the various forms of cell therapy currently available, their utility in the management of IMIDs and emerging evidence for efficacy in severe psoriasis that is unresponsive to biological therapy. Balancing the risks and benefits of treatment vs. the underlying disease is key; cell therapy carries significant risks, costs, regulation and other complexities, which must be justified by outcomes. Although HSCT has anecdotally been reported to benefit severe psoriasis, sometimes with apparent cure, this has mainly been in the setting of other coincidental 'routine' indications. In psoriasis, cell therapies, such as MSC and regulatory T cells, with a lower risk of complications are likely to be more appropriate. Well-designed controlled trials coupled with mechanistic studies are warranted if advanced cell therapies are to be developed and delivered as a realistic option for severe psoriasis.

Introduction

Psoriasis is a common, immune-mediated inflammatory disease (IMID) with significant morbidity and detrimental impact on the affected individual's quality of life. It is associated with important medical conditions, including psoriatic arthritis (PsA), metabolic syndrome, depression and cardiovascular disease; people with psoriasis have a higher mortality than the general population.[1] The complex interplay between genetic, epigenetic, immune and environmental factors that underlie the disease pathogenesis is not fully understood.[2] However, the emergence of biological therapies targeting key immune pathways in psoriasis pathogenesis, such as tumour necrosis factor (TNF)-α, interleukin (IL)-17 and IL-23, has revolutionized the treatment landscape of severe disease. These therapies can lead to significant improvement in disease burden and quality of life for people with psoriasis. However, targeted therapies are not curative; their limitations include lack of clinical response in certain individuals, diminishing efficacy over time and occasional significant adverse effects.[3] Consequently, there is an increasing number of patients with psoriasis who are refractory to multiple lines of biological and nonbiological systemic therapies. This underscores an urgent and increasing need for more advanced, perhaps curative, treatment options including nonpharmaceutical approaches for severe psoriasis.

Cell therapy comprises the use of somatic cells (stem, progenitor or primary cells) isolated from either the affected individual (autologous) or a donor (allogeneic) to treat the underlying disease. The various types of somatic cells that are used, or have the potential to be used, as cell therapy in IMIDs include haematopoietic stem cells (HSCs), mesenchymal stem or stromal cells (MSCs), multilineage-differentiating stress-enduring (Muse) cells, fibroblasts, induced pluripotent stem cells (iPSCs), regulatory T cells (Tregs) and chimeric antigen receptor (CAR)-T cells. The last two decades have witnessed rapid advances in clinical trials and commercialization of cell therapy, for which the three most common disease indications in Europe between 2004 and 2014 were cancer, cardiovascular disease and connective tissue diseases.[4] Observations of serendipitous 'transfer' and 'cure' of IMIDs after HSC transplantation (HSCT) have raised interest in the potential of cell therapy as an option for these conditions with a number of controlled and open studies mainly in multiple sclerosis (MS), musculoskeletal disease and systemic sclerosis (SS). Similar observations of 'transfer' and 'cure' have been made for psoriasis over the years, but there are few subsequent hypothesis-testing studies. Thus, there appears to be a rationale and an impetus to explore the use of cell therapy in psoriasis, specifically for patients who are refractory to currently available therapies.

This review discusses the following three key aspects of cell therapy: (i) types of cell therapy for IMIDs; (ii) accumulated data on the use of cell therapy in the management of psoriasis; and (iii) the future direction of cell therapy for psoriasis.

processing....