Tolerogenic Cell-Based Therapy: Where We Stand?
A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".
Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 29276
Special Issue Editor
Interests: HLA-G; vitamin D3
Special Issues, Collections and Topics in MDPI journals
Special Issue Information
Dear Colleagues,
The development of novel approaches to control unwanted immune responses represents an ambitious goal in the management of a number of clinical conditions, including autoimmunity, autoinflammatory diseases, organ and cell transplantation allergies, and replacement therapies, in which the T-cell response to self, allogeneic, and nonharmful antigens threatens the physiological function of tissues and organs. Current treatments for these conditions rely on the use of nonspecific immunosuppressive agents and supportive therapies, which may efficiently dampen inflammation and compensate for organ dysfunction, but they require lifelong treatments not devoid of cumbersome side effects. These limitations induced researchers to undertake the development of definitive and specific solutions to these disorders: The underlying principle of the novel approaches relies on the idea that empowering the tolerogenic arm of the immune system would restore the balance and control the disease.
Cell-based therapies are clinically attractive for promoting or restoring tolerance in T-cell-mediated diseases, as they can theoretically control several inflammatory cells, including T and B lymphocytes, NK cells and APCs, leading to the control of unwanted immune responses. Therapies based on adoptive transfer of regulatory cells (T, macrophages, and tolerogenic (tol)DC) entered the clinical arena in recent years with the goal to investigate the safety and feasibility of the approach, and several studies are still ongoing.
Despite encouraging results, a number of open questions remain before regulatory-based therapies can be routinely used to prevent graft rejection and to treat or cure autoimmune diseases. Several open questions remains to be tackled when designing tolerogenic-based therapies: i) their potential to mediate pan immunosuppression in vivo, due to the phenomenon of bystander immune suppression; ii) the stability of the cell product to be infused must be evaluated for limiting in vivo side effects or disease exacerbation; iii) the overall impact of long-lasting tolerogenic cells on infections and malignancies; iv) the necessity of multiple cell infusions to allow the induction of the self-sustained mechanisms described above will invariably lead to high manufacturing costs; iv) the expansion/generation of autologous tolerogenic cells implies the use of patient-derived cells, which may not be as functional as those isolated from healthy subjects.
The purpose of this Research Topic is to define the current advances in understanding the tolerogenic treatments based on cell products to modulate immune tolerance or autoimmunity. For this purpose, we particularly encourage studies on animal disease models or clinical trials, which will contribute to the future development of clinical treatments using tolerogenic cells to target human diseases.
Dr. Silvia Gregori
Guest Editor
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Keywords
- tolerance
- cell-based therapy
- autoimmune diseases
- organ transplantation
- graft-versus host disease
- regulatory T cells
- tolerogenic DC
- immunoregulation
