Research Topic

Emerging Therapeutics for Immune Tolerance

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Autoimmune diseases affect roughly 5-10% of total population, with women affected more than men. The standard treatment for autoimmune or autoinflammatory diseases had long been immunosuppressive agents, until the advent of biologic drugs, which aimed at blocking inflammatory cytokines and mediators of ...

Autoimmune diseases affect roughly 5-10% of total population, with women affected more than men. The standard treatment for autoimmune or autoinflammatory diseases had long been immunosuppressive agents, until the advent of biologic drugs, which aimed at blocking inflammatory cytokines and mediators of inflammation. At the frontier of these biologic drugs are TNFa blockers. The anti-TNFa therapy aims at reversing the action of TNFa in common autoimmune diseases such as rheumatoid arthritis (RA). This quickly became the standard of care for these diseases due to their effectiveness in controlling diseases and decreasing patient’s risk profiles. However, anti-TNF therapies have limitations. First, there are still great unmet needs for patients who are refractory, or who become unresponsive to the therapy. Second, they provide remedies to relieve the symptoms, but do not provide the cure by removing the root cause of the diseases. Third, they still have safety risks, either increasing susceptibility to opportunistic infections or malignancies, or causing multiple side effects. Thus, the next wave of truly transformative therapeutics should aspire to provide a cure by selectively suppressing autoantigen-specific immune responses while leaving the rest of immune system intact for the control of infection or malignancies.

Therapeutics that induce, restore and maintain immune tolerance towards autoantigens represent the Holy Grail of treatments. Novel therapeutics with different modalities have been emerging and are being tested in clinics to achieve immune tolerance in various autoimmune diseases. Most of these novel therapeutics harness the mechanism of immune tolerance, such as increasing antigen-specific or polyclonal Foxp3+Treg specifically as they play a fundamental role in establishing immune tolerance or inducing anergy or deletion of pathologic immune cells. Among those therapeutics, we would like to focus on four main areas of active research in immune tolerance in this Research Topic. First, tolerogenic vaccines aiming at autoantigen-specific immune tolerance. Second, cell therapies either using polyclonal or autoantigen-specific regulatory T cells, chimeric antigen receptor (CAR)- expressing regulatory T cells as well as chimeric autoantigen receptor (CAAR)- expressing T cells, or dendritic cell vaccines. Third, Immunotherapies aiming at inactivating T cells either by antagonizing costimulatory receptors, or agonizing coinhibitory receptors, or inducing anergy. Fourth, therapeutics aiming at expanding regulatory T cell specifically.

Thus, this Research Topic welcomes Original Research, Mini Review, Perspective, Opinion and General Commentary articles which explore, but are not limited to, the following sub-topics:
• Tolerogenic vaccines to achieve antigen-specific tolerance
• Cell therapy for immune tolerance
• Immunotherapies to inactivate T cells utilizing costimulatory receptor or anti-CD3 blockade or agonizing coinhibitory receptors
• Immune tolerance using therapeutics to induce Foxp3+ regulatory T cells using low dose IL-2 or IL-2 derivatives such as IL-2 mutein


Dr. Phee is an employee of Amgen and Dr. Moon is the Co-Founder and Chief Scientific Officer of EVOQ Therapeutics. The other Topic Editors declare no conflicts of interest with regard to this topic.


Keywords: immune tolerance, tolerogenic vaccines, Foxp3+Tregs, tolerance therapeutics, IL-2


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