Pilot Study of Delayed ICOS/ICOS-L Blockade With αCD40 to Modulate Pathogenic Alloimmunity in a Primate Cardiac...

Area of Science:

• Immunology
• Transplantation immunology
• Allograft rejection

Background:

• Inducible costimulator (ICOS) is upregulated with T-cell stimulation and may be an alternative costimulation pathway.
• Rodent models suggest ICOS blockade may prevent chronic rejection, but efficacy in primates is unknown.

Purpose of the Study:

• To determine if ICOS-Ig treatment prolongs cardiac allograft survival in non-human primates (NHPs).
• To assess if ICOS-Ig treatment attenuates pathogenic alloimmunity when combined with CD40 blockade.

Main Methods:

• Cynomolgus monkeys received cardiac allografts and were treated with anti-CD40 (d0-90) alone or with delayed ICOS-Ig (d63-110).
• Allograft survival, rejection scores, and alloantibody production were monitored.

Main Results:

• Median allograft survival was similar between groups (120 days vs. 124 days).
• Delayed ICOS-Ig treatment did not prevent rejection, despite reducing CD4+ T-effector memory cells.
• Acute and chronic rejection scores and alloantibody kinetics were comparable between groups.

Conclusions:

• Delayed ICOS-Ig treatment, as tested, appears ineffective in modulating primate alloimmunity.
• ICOS blockade may not be a viable strategy for preventing transplant rejection in non-human primates.