Identifying common ground: immune modulating therapeutics with applications across solid organ transplant and gene therapy

Immune modulating therapeutics have applications across solid organ transplant and gene therapy. Immune suppression therapeutics (e.g. calcineurin inhibitors, antiproliferatives, mTOR inhibitors, corticosteroids, biological induction agents such as anti-thymocyte globulin[rATG], co-stimulation blockade such as belatacept, and anti-complement/anti-humoral agents) are routinely used in the field of solid organ transplant to achieve lifelong tolerance. Chronic, systemic, administration of immunosuppressants (IS) can result in multiple side effects including high incidence of various types of infections, malignancy, renal toxicity, negative etiologies that impact metabolic, cardiovascular, gastrointestinal, musculoskeletal, and neurological. As such, there are now novel therapeutics approaches that utilize gene therapy platforms to tolerize solid organs for transplant and mitigate the chronic application of systemic IS drugs.

Compared to solid organ transplant the gene therapy field is still in its infancy. Many of the IS therapeutics that had their proving grounds in solid organ transplant have also found applications in the gene therapy field. In typical gene therapy protocols IS therapeutics can be applied for transient immune dampening around the time of vector delivery. Multiple IS therapeutics have been applied in gene therapy clinical protocols. In fact, some of these therapeutics have become standard-of-care to evade severe immune response to the delivery vehicle and therapeutic transgene. Importantly, gene therapy protocols that may require redosing (i.e. for Duchenne muscular dystrophy or hemophilia) will require immune suppression intervention.

Systemic delivery of immunosuppression therapeutics can lead to numerous negative biological outcomes. This Research Topic is intended to build an understanding of approaches to mitigate the use of these IS therapeutics for transplant and gene therapy. We invite researchers across the biotechnology industry, academics, and government for Original Research and Reviews that work at the immune intersection for gene therapy or solid organ transplant, and those that utilize gene therapy to address chronic delivery of IS during transplant. Manuscripts could address how to mitigate antibody and cell-mediated immune responses that exist prior to transplant and gene therapy and post-transplant and gene therapy administration.

Topics of interest include:
• Approaches to mitigate pre-existing cell-mediated immune responses during transplant or gene therapy protocols
• Approaches to mitigate pre-existing antibody responses during transplant or gene therapy protocols
• Approaches to mitigate SoC IS protocols through use of gene therapy for solid organ transplant
• Approaches to mitigate use of SoC IS protocols for gene therapy
• Novel approaches to mitigate adaptive immune responses to confer redosing for gene therapy recipients

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• Case Report
• Classification
• Clinical Trial
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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
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Calcineurin inhibitors, Anti-thymocyte globulin, Immune tolerance induction, Solid organ transplant rejection, Gene therapy immunogenicity, AAV vector immune response, Costimulation blockade, Belatacept, Transgene immunogenicity, Redosing gene therapy, Pre-existing anti-vector antibodies, Alloimmune response, Immunosuppression-sparing strategies, Cell-mediated alloimmunity, Humoral rejection mitigation

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