Autoimmunity reviews | 2021
Safety and immunological proof-of-concept following treatment with tolerance-inducing cell products in patients with autoimmune diseases or receiving organ transplantation: A systematic review and meta-analysis of clinical trials.
Abstract
In the past years, translational approaches have led to early-stage clinical trials assessing safety and efficacy of tolerance-inducing cell-based treatments in patients. This review aims to determine if tolerance-inducing cell-based therapies, including dendritic cells, regulatory T cells and mesenchymal stem cells, are safe in adult patients who underwent organ transplantation or in those with autoimmune diseases, including multiple sclerosis, diabetes mellitus type 1, Crohn s disease and rheumatoid arthritis. Immunological and clinical outcomes were reviewed, to provide evidence for proof-of-concept and efficacy. To summarize the current knowledge, a systematic review and meta-analysis were conducted. A total of 8906 records were reviewed by 2 independent assessors and 48 records were included in the final quantitative analysis. The overall frequency of serious adverse events was low: 0.018 (95% CI: 0.006-0.051). Immunological outcomes could not be assessed quantitatively because of heterogeneity in outcome assessments and description as well as lack of individual data. Most randomized controlled studies were at a medium risk of bias due to open-label treatment without masking of assessors and/or patients to the intervention. In conclusion, tolerance-inducing cell-based therapies are safe. We advocate for harmonization of study protocols of trials investigating cell-based therapies, adverse event reporting and systematic inclusion of immunological outcome measures in clinical trials evaluating tolerance-inducing cell-based treatment. Registration: PROSPERO, registration number CRD42020170557.