Use of polyclonal/monoclonal antibody therapies in transplantation

ABSTRACT

Introduction: For over thirty years, antibody (mAb)-based therapies have been a standard component of transplant immunosuppression, and yet much remains to be learned in order for us to truly harness their therapeutic capabilities. Current mAbs used in transplant directly target and destroy graft-destructive immune cells, interrupt cytokine and costimulation-dependent T and B cell activation, and prevent down-stream complement activation.

Areas covered: This review summarizes our current approaches to using antibody-based therapies to prevent and treat allograft rejection. It also provides examples of promising novel mAb therapies, and discusses the potential for future mAb development in transplantation.

Expert opinion: The broad capability of antibodies, in parallel with our growing ability to synthetically modulate them, offers exciting opportunities to develop better biologic therapeutics. In order to do so, we must further our understanding about the basic biology underlying allograft rejection, and gain better appreciation of how characteristics of therapeutic antibodies affect their efficacy.

KEYWORDS:

• Acute cellular rejection
• antibody mediated rejection
• antithymocyte globulin
• alemtuzumab
• basiliximab
• belimumab
• eculizumab
• induction therapy
• monoclonal antibodies
• rATG
• rituximab
• TOL101
• tocilizumab
• transplantation
• transplant rejection
• Thymoglobulin

Article highlights

• mAbs currently used in transplant directly target and destroy graft-destructive immune cells (ATG, alemtuzumab, rituximab), interrupt cytokine and costimulation-dependent T and B cell activation (IL2RA), and prevent down-stream complement activation (eculizumab)

• Induction regimens are often decided on a case-by-case basis, but in general, lymphocyte-depleting agents (ATG, alemtuzumab) are used in high-immunological risk cases and in steroid-sparing protocols, whereas IL2RA is commonly used in low-immunological risk patients. However, the optimal induction regimen remains controversial.

• For severe (Banff grade IB and above) or refractory acute cellular rejection, mAb-based depletion therapies (ATG, alemtuzumab) are often used.

• For antibody-mediated rejection, rituximab (B cell depleting mAb) and eculizumab (anti-C5a complement inhibitor) have shown efficacy.

• A number of novel mAb-based therapies are currently being investigated for use in transplantation, including belimumab (anti-Blys), tocilizumab (IL6RA), and TOL101 (anti-TCR)

• To develop better mAb-based therapeutics for use in transplant, we must not only improve our understanding about the basic biology underlying allograft rejection, but also focus on understanding how characteristics of therapeutic antibodies may enhance their clinical efficacy.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties

Additional information

Funding

This manuscript has not been funded.