Abstract
Regulatory Tcells (Treg) are essential components of peripheral immune homeostasis. Adoptive Treg cell therapy has shown efficacy in a variety of immune-mediated diseases in preclinical studies and is now moving from phase I/IIa to larger phase II studies aiming to demonstrate efficacy. However, hurdles such as in vivo stability and efficacy remain to be addressed. Nevertheless, preclinical models have shown that Treg function and specificity can be increased by pharmacological substances or gene modifications, and even that conventional T cells can be converted to Treg potentially providing new sources of Treg and facilitating Treg cell therapy. The exponential growth in genetic engineering techniques and their application to T cells coupled to a large body of knowledge on Treg open numerous opportunities to generate Treg with “superpowers”. This review summarizes the genetic engineering techniques available and their applications for the next-generation of Super-Treg with increased function, stability, redirected specificity and survival.
Highlights
The immune system has developed physiological regulatory mechanisms to avoid excessive intensity or duration of immune responses and inflammation
Undesired immune reactivity needs to be controlled in pathological situations such as autoimmune diseases, solid organ transplantation (SOT), graft-vs.-host disease (GvHD), and immunogenicity of gene therapeutics and biologics
Functional CD4+ Treg from IPEX patients could be obtained by ectopic expression of FOXP3 in their Tconv [26], and with more clinical potential by precise homology directed repair (HDR) on hematopoietic stem cells [27] (Table 1)
Summary
The immune system has developed physiological regulatory mechanisms to avoid excessive intensity or duration of immune responses and inflammation. G−retroviral vector Human FOXP3 gene in CD4+ Tconv cells, lentiviral production Foxp3 overexpression in CD4+ Tconv with or without Only with antigen-specific CD4 cells but not islet specificites, g−retroviral vector polyclonal CD4+ FOXP3+ controlled recent onset diabetes despite similar suppression in vitro (Continued)
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