Articles tagged "Co-stimulation"

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…
2018 American Transplant Congress
Loss of HIF-1α in CD4 T Cell Improve Outcome of Mouse Vascularized Osteomyocutaneous Allotransplantation under Costimulation Blockade
C-.H. Lin,^1,2 M. Anggelia,^1,2 H. Yang,³ W. Chuang,⁴ H. Cheng,¹ F-.C. Wei,^1,2 G. Brandacher.⁵
¹PRS, Center for VCA, Chang Gung Memorial Hospital, Taoyuan, Taiwan; ²Chang Gung Medical College and Chang Gung University, Taoyuan, Taiwan; ³Nephrology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; ⁴Pathology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; ⁵PRS, Johns Hopkins University School of Medicine, Baltimore, MD.
Background: Allograft survival depends on the balance of effector T cells (Teff) and regulatory T cells (Tregs). Previous study suggested that the balance is controlled…
2018 American Transplant Congress
Thymic Irradiation as a Maneuver for Repertoire Exchange in Costimulatory-Blockade-Based Immunotherapy
M. Mulvihill,¹ B. Ezekian,¹ Q. Gao,¹ K. Samy,¹ R. Davis,¹ F. Leopardi,¹ W. Giles,² F-.F. Yin,² C. Willett,² B. Collins,¹ A. Kirk.¹
¹Department of Surgery, Duke University, Durham, NC; ²Department of Radiation Oncology, Duke University, Durham, NC.
Background All successful, prospective clinical tolerance-induction strategies have employed thymic irradiation to achieve chimerism. However, evidence suggests durable chimerism is not required to attain tolerance.…
2018 American Transplant Congress
Graft Dendritic Cell p40 Homodimers Activate Donor-Reactive Endogenous Memory CD8 T Cells within Higher Risk Allografts
H. Tsuda, A. Valujskikh, R. Fairchild.
Immunology, Cleveland Clinic, Cleveland, OH.
Memory T cells with donor-reactivity pose a major barrier to successful allograft transplantation and tolerance induction. Longer cold ischemic storage (CIS) prior to transplantation promotes…
2018 American Transplant Congress
p40 Homodimer Induced Proliferation of Endogenous Donor-Reactive Memory CD8 T Cells within High Risk Allografts Requires Memory CD8 T Cell Expression of CD122
H. Tsuda, A. Valujskikh, R. Fairchild.
Immunology, Cleveland Clinic, Cleveland, OH.
Increasing the duration of cold ischemic storage (CIS) from 0.5 to 8 hrs prior to transplant induces the increased proliferation of endogenous donor-reactive CD4 and…
2018 American Transplant Congress
The BEST Trial: A Prospective Randomized Multicenter Trial of Belatacept-Based CNI- and Corticosteroid-Free Immunosuppression
E. Woodle,¹ D. Kaufman,² A. Shields,¹ J. Leone,³ A. Wiseman,⁴ A. Matas,⁵ P. West-Thielke,⁶ E. King,¹ R. Alloway.¹
¹U Cincinnati, Cincinnati; ²U Wisconsin, Madison; ³Tampa General, Tampa; ⁴U Colorado, Denver; ⁵U Minnesota, Minneapolis; ⁶UIC, Chicago.
Previous large multicenter belatacept (BELA)-based CNI- and steroid-free immunosuppressive trials have not enrolled to completion due to safety concerns. The BEST Trial (Belatacept-based Early Steroid…
2018 American Transplant Congress
Late Conversion from Calcineurin Inhibitors to Belatacept is Associated with a Sustained Improvement in Kidney Allograft Function
S. Sethi, J. Choi, A. Vo, R. Najjar, A. Peng, S. Jordan, E. Huang.
Medicine/Nephrology, Cedars Sinai Medical Center, Los Angeles, CA.
Introduction: Belatacept was shown to have longer kidney graft survival and higher eGFR at 7 years than a calcineurin inhibitor (CNI)-based regimen in the BENEFIT…