P904 Aims: The β1 integrin very late antigen-4 (VLA-4) is a key adhesion molecule involved in lymphocyte-endothelial cell rolling and firm adhesion, and lymphocyte migration through adhesion to extracellular matrix proteins. Blockade of cell-cell and cell-matrix interactions have been used extensively to modulate immune response and graft rejection. In this study, we evaluated the combined use of WAY-160279, a VLA-4 antagonist, with sirolimus in a model of vascularized heart allograft in the rat. Methods: Heterotopic heart transplantation was performed. Rat recipients were treated with WAY-160279 orally twice daily (10-50 mg/kg) in combination with low doses of sirolimus, for 14 days posttransplantation. Drug interaction between WAY-160279 and sirolimus was assessed using median-effect principle and combination index (CI). Results: WAY-160279 monotherapy slightly prolonged cardiac allograft survival compared to untreated group (P<0.05). Nevertheless, five different combinations of low doses of WAY-160279 and sirolimus synergistically extended cardiac allograft survival for up to 45 days posttransplantation (P<0.001; CI = 0.174-0.970). Conclusion: We have demonstrated that a concomitant use of WAY-160279 with sirolimus prolongs cardiac allograft survival in the rat. This initial study warrants further evaluation in this drug combination in larger animal models.