Articles tagged "Co-stimulation"

2016 American Transplant Congress
Acute Rejection in Non-Human Primates Treated with Belatacept Is Mediated by a Unique CD8 Memory Subset.
D. Mathews,¹ W. Wakwe,¹ M. Lowe,¹ C. Breeden,¹ F. Leopardi,¹ A. Farris,¹ M. Song,¹ E. Strobert,² J. Jenkins,² C. Larsen,¹ R. Townsend,³ A. Adams.¹
¹Emory Transplant Center, Emory University, Atlanta, GA; ²Yerkes National Primate Research Center, Atlanta, GA; ³Bristol Myers-Squibb Pharmaceutical Research Institute, Princeton, NJ.
Belatacept is a high affinity version of the fusion protein CTLA4-Ig that blocks CD28 mediated T cell costimulation, providing a more targeted/less toxic form of…
2016 American Transplant Congress
Profiling of T Cell Subsets in a Primate Cardiac Transplant Model.
N. O'Neill, T. Zhang, G. Braileanu, W. Sun, X. Cheng, C. Evans, R. Pierson, A. Azimzadeh.
Surgery, University of Maryland, Baltimore, MD.
Purpose: Costimulation blockade prolongs graft survival but does not induce tolerance in primates, and mechanisms of rejection are incompletely understood. Here we evaluate changes in…
2016 American Transplant Congress
Vascularized Composite Allograft Tolerance with Transient High-Dose Tacrolimus Across a Full MHC Mismatch in a Large Animal Model.
H. Wang, E. Swanson, H.-T. Cheng, J. Walch, J. Alonso-Esclante, K. Kolegraff, J. Lopez, G. Furtmuller, B. Oh, A. Quan, J. Budihardjo, S. AlFadil, S. Mulla, P. Akre, J. Sacks, S. Bonawitz, G. Raimondi, J. Shores, D. Cooney, W. Lee, G. Brandacher.
Department of Plastic Surgery, Johns Hopkins University, Baltimore, MD.
PURPOSE: Vascularized composite allografts (VCA) can enhance the quality of life of patients with severe facial or extremity injuries, and the induction of tolerance would…
2016 American Transplant Congress
Avoidance of CNI and Steroids Using Belatacept – A Preliminary Report of CTOT-16.
R. Mannon,¹ P. Stock,² A. Mehta,³ D. Ikle,⁴ N. Watson,⁵ N. Bridges,⁵ M. Robien,⁵ K. Newell.³
¹UAB, Birmingham; ²UCSF, San Francisco; ³Emory, Atlanta; ⁴Rho, Chapel Hill; ⁵NIAID, Bethesda.
CTOT-16 tested the hypothesis that belatacept used as maintenance immunosuppression (IS) in kidney transplantation would allow the long-term avoidance of CNI and corticosteroids. Methods: Primary…
2016 American Transplant Congress
Anti-BTLA Antibody (6B2) Induced Prolongation of Fully MHC-Mismatched Murine Cardiac Allograft and Generation of Foxp3+ Regulatory T Cells.
M. Uchiyama,^1,2 E. Yin,^2,3 X. Jin,^2,4 T. Shimokawa,¹ H. Yagita,⁵ M. Niimi.²
¹Cardiovascular Surgery, Teikyo University, Tokyo, Japan; ²Surgery, Teikyo University, Tokyo, Japan; ³Cardiovascular Surgery, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China; ⁴Thoracic Surgery, The 3rd Affiliated Hospital of Harbin Medical University, Harbin, China; ⁵Immunology, Juntendo University Hospital, Tokyo, Japan.
Background: The co-inhibitory receptor B and T lymphocyte attenuator (BTLA; CD272) has been implicated in the regulation of autoimmune and may potentially play an important…
2016 American Transplant Congress
Examining the Risk for Post-Transplant Viral Infections and Lymphoproliferative Disorder (PTLD) in Kidney Transplant Patients (Pts) Receiving Calcineurin Inhibitor-Based Immunosuppression (CNI-IS) Compared to Belatacept (CTLA4Ig).
B. Shin, J. Choi, J. Kahwaji, S. Ge, D. Thomas, A. Vo, O. Galera, R. Villicana, A. Peng, S. Jordan, M. Toyoda.
Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.
Introduction: CTLA4Ig is a novel IS agent that acts through costimulatory blockade of T-cells and obviates the need for CNI. Despite benefits in improving renal…
2016 American Transplant Congress
Belatacept Immunotherapy Is Not Augmented by Blockade of Activated LFA-1 in a Nonhuman Primate Renal Transplant Model.
K. Samy,¹ M. Mulvihill,¹ B. Collins,¹ D. Lo,² M. Song,¹ F. Leopardi,¹ A. Kirk.^1,2
¹Department of Surgery, Duke University Medical Center, Durham, NC; ²Emory University, Atlanta, GA.
Purpose: Belatacept specifically targets de novo alloimmune responses without off target side effects. However, resistant alloreactive memory T cells have complicated its use. LFA-1 therapy…
2016 American Transplant Congress
Tracking of Endogenous Graft-Reactive Tregs Reveals Their Peripheral Enrichment During Transplantation Tolerance.
J. Young,¹ J. Chen,¹ M. Miller,¹ D. Yin,¹ J. Moon,² M.-L. Alegre,¹ A. Chong.¹
¹Surgery and Medicine, University of Chicago, Chicago, IL; ²Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA.
Purpose: Our goal for this study was to determine the relative fates of endogenous Foxp3- conventional (Tconv) and Foxp3+ regulatory T cells (Tregs) specific for…
2016 American Transplant Congress
The BEST Trial: A Prospective Randomized Trial of Belatacept-Based, CNI- and Corticosteroid-Free Immunosuppression.
E. Woodle,¹ D. Kaufman,² A. Shields,¹ J. Leone,³ A. Matas,⁴ A. Wiseman,⁵ P. Thielke,⁶ R. Alloway.¹
¹U Cincinnati, Cinci; ²U Wisconsin, Madison; ³Tampa General, Tampa; ⁴U Minnesota, Minn; ⁵U Colorado, Denver; ⁶U Illinois Chicago, Chic.
Efficacy of CNI- and corticosteroid-free immunosuppressive regimens has not been demonstrated in large, multicenter trials. BEST (Belatacept-based Early Steroid Withdrawal Trial) (NCT 01729494) compares 2…
2016 American Transplant Congress
Role of Regulatory T Cells in Induction of Tolerance in Mouse Vascularized Osteomyocutaneous Allotransplantation Under Combined Costimulation Blockade.
M. Anggelia,¹ H.-Y. Cheng,¹ Y.-L. Wang,¹ W.-Y. Chuang,¹ C.-H. Lin,¹ G. Brandacher,² F.-C. Wei,¹ C.-H. Lin.¹
¹Center for Vascularized Composite Allotransplantation, Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; ²Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Baltimore, MD.
Background: The role of regulatory T cells (Tregs) in allograft tolerance has been studied using various transplant models, but the mechanism in vascularized composite allotransplantation…