Abstract
Clinical studies with cellular therapies using tolerance-inducing cells, such as tolerogenic antigen-presenting cells (tolAPC) and regulatory T cells (Treg) for the prevention of transplant rejection and the treatment of autoimmune diseases have been expanding the last decade. In this perspective, we will summarize the current perspectives of the clinical application of both tolAPC and Treg, and will address future directions and the importance of immunomonitoring in clinical studies that will result in progress in the field.
Highlights
The number of patients with autoimmune diseases, severe allergies and recipients of organ or stem cell transplants is increasing worldwide
Several protocols to generate and administer tolerogenic antigen-presenting cells (tolAPC) have been tested in phase I clinical trials with highly encouraging results from a safety point of view and in terms of adverse effects (Table 1)
It would be of great help to analyze critical pathways contributing to programming and function of tolAPC
Summary
The number of patients with autoimmune diseases, severe allergies and recipients of organ or stem cell transplants is increasing worldwide. To advance tolerogenic therapy with antigen-presenting cells (APC), we should stand on the shoulders of these pioneers and address remaining challenges, such as the optimal dose, injection route, frequency of administration, antigen-specificity, and the related issue of suitable biomarkers of cell therapyinduced reduction of general inflammatory state and induction of tolerance, in the design of the next-generation clinical trials Both tolDC and Mreg can be generated in vitro starting from CD14+ monocytes and share some phenotypic and functional characteristics. Different strategies to generate stable tolAPC have been explored, including treatment with pharmacological agents or cocktails of immunomodulatory cytokines, genetic engineering, and exposure to apoptotic cells [9, 27, 28] Most of these in vitro conditioning regimens aim at stabilizing a semi-mature state of tolDC, maintaining the capacity to induce immune hyporesponsiveness of T cells, even in presence of powerful pro-inflammatory signals. Gene expression studies comparing different tolDC and Mreg protocols have not been able to identify common biomarkers of tolerance induction [reviewed by [52, 53] and [54]]
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