CAR-T cells in systemic sclerosis.

Systemic sclerosis (SSc) is a complex disease with extensive fibrosis, microvasculopathy, and autoantibodies. Activation of the adaptive immune system involving T cells, B cells, and macrophages along with microvasculopathy is considered early events in disease pathogenesis. Today, immunosuppressives, including anti-B cell biologics, form the foundation of SSc treatment; however, significant therapeutic needs remain unmet. Autologous chimeric antigen receptor (CAR)-T cells, targeting B cell CD19 and inducing deep depletion of B cells, were tested in a few patients with SSc, leading to improvement of skin score, arthritis, digital ulcers, and inflammatory changes in heart and lungs. However, regression of lung fibrosis remains a major therapeutic challenge. In addition, autologous CAR-T cells are a personalized treatment that requires a specialized setting, is not readily available, is costly, and is associated with serious adverse effects, including cytokine release syndrome, neurotoxicity, and increased risk of infection. New developments in CAR T cell technology, including off-the-shelf allogeneic CAR T cells, bispecific CAR-T cells, and CAR NK cells, are being tested in patients with progressive refractory SSc. Key Points • There is unmet therapeutic need for systemic sclerosis(SSc). • Autologous CAR-T cells targeting CD19 showed efficacy in SSc, but are a personalized, expensive and not readily available treatment. • Off-the-shelf allogeneic CAR-T cells and CAR-NK cells are being evaluated in SSc.