Improving outcomes in scleroderma: recent progress of cell-based therapies

Abstract

Scleroderma is a rare, potentially fatal, clinically heterogeneous, systemic autoimmune connective tissue disorder that is characterized by progressive fibrosis of the skin and visceral organs, vasculopathy and immune dysregulation. The more severe form of the disease, diffuse cutaneous scleroderma (dcSSc), has no cure and limited treatment options. Haematopoietic stem cell transplantation has emerged as a potentially disease-modifying treatment but faces challenges such as toxicity associated with fully myeloablative conditioning and recurrence of autoimmunity. Novel cell therapies-such as mesenchymal stem cells, chimeric antigen receptor-based therapy, tolerogenic dendritic cells and facilitating cells-that may restore self-tolerance with more favourable safety and tolerability profiles are being explored for the treatment of dcSSc and other autoimmune diseases. This narrative review examines these evolving cell therapies.

Keywords: cell transplantation; haematopoietic; immunotherapy; scleroderma and related disorders; skin; stem cell.

Figure 1.

The modified allogeneic HSCT FCR001. FCR001 is a proprietary blend of three cell types: (i) haematopoietic stem cells, progenitor cells used to rebuild the haematopoietic immune system of the recipient, (ii) facilitating cells, a mixed population of CD8⁺/TCR⁻ cells that aid fast and efficient engraftment of donor HSCs to promote chimerism, and (iii) αβTCR⁺ T cells, a cell type that supports donor HSC engraftment but is also known to increase the risk of acute GvHD in the recipient. FCR001 utilizes an optimized number of αβTCR⁺ T cells in order to promote HSC engraftment while minimizing the risk of acute GvHD. GvHD: graft-vs-host disease; HSC: haematopoietic stem cell; HSCT: HSC transplant; TCR: T cell receptor