Articles tagged "Co-stimulation"

2018 American Transplant Congress
Preemptive B Cell Depletion Modulates Pathogenic Alloimmunity Associated with Selective Non-Activating CD28 Blockade
N. O'Neill,¹ T. Zhang,¹ W. Sun,¹ G. Braileanu,¹ X. Cheng,¹ I. Tatarov,¹ W. Hassanein,¹ Z. Habibabady,¹ B. Cerel,¹ K. Reimann,² A. Azimzadeh,¹ R. Pierson.¹
¹Surgery, University of Maryland School of Medicine, Baltimore, MD; ²University of Massachusetts Medical School, Boston, MA.
Purpose: Because anti-donor alloantibody (alloAb) elaboration is associated with chronic allograft rejection, peri-transplant B cell depletion is being explored to modulate pathogenic alloimmunity. Here, we…
2018 American Transplant Congress
Recipient IFNAR1 Signaling Supports Costimulation Independent Rejection by Promoting T Cell Activation
D. Mathews, A. Ghosh, Y. Dong, K. Polireddy, A. Stephenson, C. Breeden, Y. Liu, A. Adams.
Department of Surgery, Emory University, Atlanta, GA.
Costimulation blockade (CoB) is a promising strategy for more targeted/less toxic transplant immunosuppression which has led to the first improvement in long-term outcomes for transplant…
2018 American Transplant Congress
Rhesus-Specific Anti-Thymocyte Globulin as an Adjuvant to Costimulatory-Blockade-Based Immunotherapy
M. Mulvihill,¹ B. Ezekian,¹ Q. Gao,¹ K. Samy,¹ R. Davis,¹ F. Leopardi,¹ A. Belli,² W. Flores,² A. Buzby,² K. Reimann,² B. Collins,¹ A. Kirk.¹
¹Department of Surgery, Duke University, Durham, NC; ²MassBiologics, University of Massachusetts Medical School, Boston, MA.
Background Belatacept targets de novo alloimmune responses with minimal off target effects in renal transplantation, though adjuvant therapy is required to control costimulation-blockade resistant rejection…
2018 American Transplant Congress
Ex Vivo Expanded Regulatory T Cells Combined with Short-Term Costimulation Blockade Prevent Rejection of Vascularized Composite Allografts
B. Oh,¹ G. Furtmüller,¹ M. Grzelak,¹ L. Vuong,² M. Iglesias,¹ M. Fryer,¹ D. Cooney,¹ W. Lee,¹ G. Raimondi,¹ G. Brandacher.¹
¹Plastic and Reconstructive Surgery, Johns Hopkins SOM, Baltimore; ²Washington University in St. Louis SOM, St. Louis.
[Background] Reconstructive transplantation represents a valid therapeutic option after devastating tissue loss. Routine clinical application, however, is hampered by the toxicity of long-term maintenance immunosuppression.…
2018 American Transplant Congress
Belatacept-Refractory CD8⁺CD28^–CD38^hi Effector/Memory T Cells Are Targeted by mTOR Inhibition Leading to a Preferential Loss of CD40L
C. Castro Rojas,¹ A. Godarova,¹ A. Rike Shields,² R. Alloway,² M. Jordan,³ E. Woodle,² D. Hildeman.¹
¹Division of Immunobiology, Cincinnati Children's Hospital, University of Cincinnati College of Medicine, Cincinnati, OH; ²Division of Transplantation, University of Cincinnati College of Medicine, Cincinnati, OH; ³Division of Bone Marrow Transplant and Immune Deficiency, Cincinnati Children's Research Foundation, Cincinnati, OH.
Calcineurin inhibitors (CNIs) and corticosteroids (CSS) have substantial untoward side effects, most notably nephrotoxicity. Consequently, the FDA approved belatacept for maintenance immunosuppression. We recently completed…
2018 American Transplant Congress
B Cell Reconstitution: 36-Month Analysis of Patients Post-Alemtuzumab Induction Followed by Belatacept-Based Immunosuppression
Q. Gao,¹ A. Mehta,² A. Guasch,² A. Ghali,² A. Kirk,¹ H. Xu.¹
¹Department of Surgery, Duke University Medical Center, Durham, NC; ²Emory Transplant Center, Emory University School of Medicine, Atlanta, GA.
Alemtuzumab induction combined with belatacept and rapamycin (ABR) maintenance immunotherapy effectively prevents costimulation blockade resistant rejection (CoBRR). We longitudinally investigated kinetics of repopulating B cell…
2018 American Transplant Congress
De Novo Belatacept in Clinical Vascularized Composite Allotransplantation
L. C. Cendales,¹ D. S. Ruch,² A. R. Cardones,³ G. Potter,⁴ J. Dooley,⁵ D. Dore,⁶ J. Orr,¹ G. Ruskin,⁶ M. Song,¹ D. Chen,⁷ A. Selim,⁷ A. D. Kirk.¹
¹Surgery, Duke University, Durham, NC; ²Orthopedics, Duke University, Durham, NC; ³Dermatology, Duke University, Durham, NC; ⁴Psychiatry and Behavioral Sciences, Duke University, Durham, NC; ⁵Anesthesiology, Duke University, Durham, NC; ⁶Psysical and Occupational Therapy, Duke University, Durham, NC; ⁷Pathology, Duke University, Durham, NC.
Most immunosuppressive regimens in vascularized composite allotransplantation (VCA) have been calcineurin inhibitor (CNI)–based. Costimulation blockade has emerged as a replacement for CNI–based regimens in kidney…
2018 American Transplant Congress
Emergence of a Costimulation-Susceptible T Cell Repertoire Post-Alemtuzumab Induction
Q. Gao,¹ A. Mehta,² A. Guasch,² L. Stempora,¹ A. Kirk,¹ H. Xu.¹
¹Department of Surgery, Duke University Medical Center, Durham, NC; ²Emory Transplant Center, Emory University School of Medicine, Atlanta, GA.
Kidney transplant patients treated with belatacept-based regimens without depletional induction have higher rates of costimulation blockade resistant rejection (CoBRR). In contrast, belatacept effectively prevents rejection…
2018 American Transplant Congress
OX40 Costimulation Prevents Induction of Foxp3⁺ Tregs through Upregulation of Novel Repressors of Foxp3 Gene Expression
X. Zhang,¹ X. Xiao,¹ P. Lan,¹ J. Li,¹ Y. Dou,¹ W. Chen,¹ N. Ishii,² S. Chen,¹ E. Taparowsky,³ X. Li.^1,4
¹Immunobiology & Transplant Research Center, Houston Methodist Hospital, Houston, TX; ²Department of Microbiology and Immunology, Tohoku University, Sendai, Japan; ³Department of Biological Sciences, Perdue University, Lafayette, IN; ⁴Department of Surgery, Weill Cornell Medical College of Cornell University, New York, NY.
Foxp3+ Tregs are essential for the induction of transplant tolerance and OX40 costimulation is known to break transplant tolerance. The exact mechanism of OX40 in…
2018 American Transplant Congress
Patients Converted to Belatacept Show Different Immunophenotyping Compared with De Novo Belatacept-Treated Patients
M. Rial,¹ F. Caro,² A. Nella,² D. Guerrieri,² L. León,¹ P. Uva,¹ E. Chuluyan,² D. Casadei.¹
¹Instituto de Nefrología, Nephrology, Buenos Aires, Argentina; ²CEFYBO, UBA, CONICET, Buenos Aires, Argentina.
The incidence of adverse clinical events mainly in early, but not late post-transplantation such as an increased rate of acute rejection precludes the use of…