Table 1.
Various immune suppression regimens used to increase islet survival.
| Immunosuppression therapy | Donor islets | Recipient nonhuman primates | MST | Reference(s) |
|---|---|---|---|---|
| Rapamycin + FTY720 + basiliximab + anti-CD154 | API | Cynomolgus monkey | >187 days | (11) |
| CTLA4-Ig + rapamycin + basiliximab + anti-CD154 | NPI | Rhesus monkey | >260 days | (12) |
| anti-IL-2R + anti-CD154 + belatacept + sirolimus (rapamycin) | NPI | Rhesus monkey | >187 days | (47) |
| CTLA4-Ig + rapamycin + anti-IL-2R + anti-CD40 | NPI | Rhesus monkey | >203 days | (48) |
| MMF + CTLA4-Ig + LFA-3-Ig + anti-IL-2R + anti-LFA-1 | NPI | Rhesus monkey | 114 days | (49) |
| ATG + CVF + rapamycin + anti-TNF + anti-CD154 (+Treg) | NPI | Rhesus | >603 days | (50) |
Rapamycin (mTOR inhibitor): FTY720 (targets the sphingosine-1-phosphate receptor 1), S1PR1 (an essential component for egress of lymphocytes from lymph organs into circulation), basiliximab (anti IL-2R inhibitor), anti-CD154 (anti-human CD154 monoclonal antibody ABI793 inhibits the interaction of CD40 receptors on antigen-presenting cells and CD154 on T cells; blocking co-stimulatory signals), anti CD40 (chimeric antibody: mouse Fab and rhesus IgG4 Fc fragments; blocks CD40 and CD154 co-stimulatory signals), MMF (mycophenolate mofetil; inhibits inosine monophosphate dehydrogenase), IMPDH (an essential enzyme for the de novo synthesis of guanine and adenine MMF and thereby prevents the proliferation of both T cells and B cells and also antibody production), LFA-3-Ig (alefacept; bindings at CD2 receptors of T cells and blocks proliferation and cytokine release), CVF (suppresses the deposition of circulating complement in an efficient manner to prevent hyperacute rejection), anti-TNF (etanercep).
T regs, regulatory T cells; API, adult porcine islets; NPI, neonatal porcine islets; MST, maximum survival time.