Localized Immunomodulation Approaches for Transplantation Tolerance

Transplantation of cells, tissues, and organs serves as an effective treatment for various disorders, including end-organ failure. Immune rejection of transplants from genetically different individuals is a major limitation of the broader application of this life-enhancing/saving treatment. Immune rejection is mitigated by lifelong use of non-specific immunosuppressive agents. Irrespective of significant progress in developing safe and effective immunosuppressive agents, considerable shortcomings exist, ranging from long-term adverse effects to the inability to control rejection effectively. The transplantation field can significantly benefit from the development of immune target-specific modulatory agents or, preferably, immunomodulatory protocols that achieve transplant tolerance and preclude the requirement for chronic use of immunosuppressive agents.

A major limitation of immunosuppressive agents is their method of delivery, which is generally systemic. Systemic administration faces two critical challenges; i) heightened off-target effects, and ii) compromised efficacy arising from insufficient therapeutic concentration of the drugs at the target tissue. Given that effective immune responses are generally localized, the prospect of delivering immunosuppressive or immunomodulatory agents in a targeted and localized manner holds the potential of being both efficacious and safe compared to systemic treatments.

This Research Topic will focus on the challenges associated with standard-of-care for pancreatic islet transplantation as a treatment for type 1 diabetes and explore cutting-edge strategies that aim to either minimize the adverse effects of immunosuppression by targeted, localized delivery or develop immunomodulatory protocols that achieve tolerance. The overarching goal for this Research Topic is to bridge existing knowledge gaps and provide a comprehensive overview of recent advances in the field of islet transplantation. We invite Review and Original Research articles, focusing on, but not limited to, the following areas:

• novel biologics and delivery platforms
• biomaterials mimicking extracellular matrix to support islet engraftment
• immunomodulatory biomaterial to establish immune privilege
• novel approaches to modulate islet graft ex vivo to evade immune rejection
• impact of transplantation sites on islet engraftment and delivery of site-specific factors to improve engraftment
• localized delivery of immunosuppressive drugs
• SC-derived and genetically modified beta cells for enhanced engraftment and immune evasion.


Dr. Haval Shirwan is founder of FasCure Therapeutics, LLC, co-founder of iTolerance Inc., and inventor on various patents related to localized immunomodulation. The other topic editors declare no competing interests with regard to the topic theme.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Allograft rejection, immunosuppression, transplant tolerance, localized immunomodulation, targeted drug delivery, islet transplantation, immunomodulatory biomaterials

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.