LF 15-0195, a novel immunosuppressive agent prevents rejection and induces operational tolerance in a mouse cardiac allograft model

Transplantation
Dejun ZhouRobert Zhong

Abstract

LF 15-0195 (LF) is a new analogue of 15-deoxyspergualin (DSG) that is less toxic and more potent than DSG. The present study was undertaken to determine (1). the dose response of LF monotherapy, (2). its ability to induce tolerance, and (3) its interaction with cyclosporine (CsA), FK 506 (FK), and rapamycin (RAPA). Varying doses of LF were administered to determine dose-dependent effects on graft survival in a C57BL/6 to BALB/c heterotopic heart allograft mouse model. Transplanting-donor and third-party skin grafts into long-term survivors were used to assess the tolerance status. CsA, FK, and RAPA were combined with LF to determine their interactive effects on graft survival. The efficacy and toxicity of LF was dose dependent. High-dose LF monotherapy (>2 mg/kg) induced donor-specific operational tolerance, but it was associated with high mortality. Simultaneous administration of high-dose calcineurin inhibitors (CsA FK) prevented tolerance induced by LF. In contrast, a short course of LF combined with a subtherapeutic dose of CsA FK achieved indefinite survival of C57/BL6 cardiac allografts. RAPA and LF had a synergistic effect in induction of tolerance. The efficacy and toxicity of LF were dose dependent. A short course of L...Continue Reading

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Citations

Mar 25, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Xusheng ZhangWei-Ping Min
Jan 16, 2007·The Journal of Hand Surgery·Julio A Clavijo-AlvarezW P Andrew Lee
May 1, 2008·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·R P RotherH Wang
Jan 24, 2007·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·L S KeanC P Larsen
Oct 4, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Justine DurandElise Chiffoleau
Jan 6, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Valérie DuplanAbdelhadi Saoudi
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May 31, 2021·The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation·Bowen WangXiufen Zheng

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