Beneficial effect of graft perfusion with anti-T cell receptor monoclonal antibodies on survival of small bowel allografts in rat recipients treated with brequinar alone or in combination with cyclosporine and sirolimus

Transplantation
M WangB D Kahan

Abstract

In the present experiments, a multimodality regimen was developed that included an anti-T cell receptor R73 monoclonal antibody and the pharmacologic agents brequinar (BQR), cyclosporine (CsA), and sirolimus (rapamycin; RAPA) to prolong the survival of small bowel (SB) allografts. BQR was the most potent single drug: the 4.0 or 8.0 mg/kg/day BQR doses delivered every second day (q.o.d.) per gavage for 28 days prolonged the survival of Brown Norway (BN; RT1n) SB allografts in Lewis (LEW; RT1l) recipients from a mean survival time of 10.6 +/- 1.9 days in untreated controls to 29.2 +/- 5.8 days, respectively (both P < 0.001). When treatment was extended to 56 days, 8.0 mg/kg/q.o.d BQR produced a mean survival time of 83.8 +/0 33.8 days (P < 0.001), with 2/5 hosts surviving more than 100 days. In a host-versus-graft model, BQR (8.0 mg/kg/q.o.d) delivered for 28 days with CsA (2.0 mg/kg/day) and RAPA (0.04 mg/kg/day) delivered intravenously for 14 days prolonged the survival of BN SB grafts in LEW recipients to 54.4 +/- 21.0 days (P < 0.001). Extending triple-drug therapy to 42 days induced the prolongation of SB allograft survival to greater than 100 days in 5/7 recipients. Although pretransplant perfusion of the grafts with R73 mA...Continue Reading

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Citations

May 14, 2003·Transplantation Proceedings·S M Stepkowski
Mar 19, 2002·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Jun MoharaYasuo Morishita
Dec 28, 1999·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·J MoharaK Matsumoto
Feb 4, 1998·Baillière's Clinical Gastroenterology·O GouletC Ricour
Feb 12, 2017·Transplantation·Yan XieJosh Levitsky
Jul 1, 1997·Journal of Pediatric Gastroenterology and Nutrition·O GouletC Ricour
Aug 14, 2002·World Journal of Gastroenterology : WJG·Xiao-Ting WuXie-Lin Feng

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