Pulsed immunosuppression with everolimus and anti-alphabeta T-cell receptor: laryngeal allograft preservation at six months.
OBJECTIVE
Laryngeal transplantation can restore the voice in patients who have undergone laryngectomy. However, the prospect of lifelong immunosuppression is a drawback to this procedure. We present data from a study aimed at minimizing the need for immunosuppression while maintaining graft viability through a novel pulsed-dosing protocol.


METHODS
Larynges were transplanted from Lewis-brown Norway (RT1(l+n, F1) rats to Lewis (RT1(l)) recipients. All recipients received 7 days of treatment with everolimus and mouse anti-rat alphabeta T-cell receptor (anti-TCR) monoclonal antibodies beginning the day before transplantation. At 90 days after transplantation, all recipients received a pulse of the same treatment combination for 5 days. From 90 to 180 days after transplantation, the rats received no treatment (group 1, n = 5), 2.5 mg/kg everolimus per day (group 2, n = 5), or 1.0 mg/kg everolimus per day (group 3, n = 5).


RESULTS
Histologic analysis of rats that received everolimus as pulse therapy evidenced no signs of rejection, whereas animals that were untreated after 90 days had normal to mild chronic rejection. T-cell reconstitution occurred 65 days after perioperative immunosuppressive treatment, but less rapidly after pulse therapy. Also, peripheral chimerism was generated in all 3 groups.


CONCLUSIONS
In the rat laryngeal transplantation model, short-term perioperative therapy with everolimus and anti-TCR followed by pulsing is a viable alternative to the concerns associated with continuous, lifelong immunosuppression.
Khariwala
Samir S
SS
Head and Neck Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Knott
P Daniel
PD
Dan
Olivia
O
Klimczak
Aleksandra
A
Siemionow
Maria
M
Strome
Marshall
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004195:Disease Models, Animal; D000068338:Everolimus; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007830:Larynx / Q000637:transplantation*; D009926:Organ Preservation / Q000379:methods*; D011300:Preoperative Care; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D016693:Receptors, Antigen, T-Cell, alpha-beta; D000068338:Everolimus; D020123:Sirolimus