Articles tagged "Co-stimulation"

2018 American Transplant Congress
CFZ533, a New Anti-CD40 mAB Demonstrates Comparable Efficacy and Better Renal Function versus Tacrolimus in De-Novo CNI-Free Kidney Transplantation
B. Nashan,¹ H. Tedesco,¹ M. van den Hoogen,¹ S. Berger,¹ D. Cibrik,¹ S. Mulgaonkar,¹ D. Leeser,¹ R. Alloway,¹ A. Patel,¹ J. Pratschke,¹ C. Sommerer,¹ A. Wiseman,¹ A. van Zuilen,¹ U. Laessing,² J. Rush,² B. Haraldsson,² O. Witzke.¹
¹CFZ533 Study Group, Basel, Switzerland; ²Novartis Pharma, Basel, Switzerland.
Purpose: To assess the potential of CFZ533 as primary immunosuppressant in a calcineurin(CNI)-free regimen in de novo kidney transplant (KTx) patients(pts).Method: CFZ533 is a new,…
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…
2017 American Transplant Congress
Anti-CD40 mAb Promotes Kidney Immunoregulatory Capacity in NHP Transplants by Altering Kidney Tubular Cell (TEC) Expression of CD40 and IL-6.
J. Arp,¹ Y. Ma,¹ H. Yang,² A. El Warrak,¹ A. Haig,¹ W. Liu,¹ K. Reimann,³ P. Luke,¹ Z. Zhang,¹ D. Rothstein,⁴ A. Jevnikar.¹
¹Medicine, Pathology & Microbiology & Immunology, Western University, London, ON, Canada; ²Sichuan Provincial Hospital, Chengdu, Sichuan, China; ³University of Massachusetts, Boston, MA; ⁴University of Pittsburgh, Pittsburgh, PA
Treatment of cynolmolgus monkey (NHP) renal transplant recipients with a combination of 2 rhesus-mouse chimeric α-CD45RB (r6G3R1; 6G3) and α-CD40 (r2C10R4; 2C10) mAbs increased circulating…
2017 American Transplant Congress
Memory T Cells Are Decreased in Transplant Recipients Deficient in miR-182.
V. Kaul, L. Wei, X. Qu, O. Martinez, S. Krams.
Transplant Immunology Lab/Division of Abdominal Transplant, Stanford University, Stanford
MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate the post-transcriptional expression of target genes. There is ample evidence that miRNAs are involved in the…
2017 American Transplant Congress
Combination αCD28+αCD40 Costimulation Blockade Attenuates Acute and Chronic Rejection in Non-Human Primates.
N. O'Neill, T. Zhang, W. Sun, G. Braileanu, X. Cheng, I. Tatarov, W. Hassanein, A. Azimzadeh, R. Pierson.
University of Maryland School of Medicine, Baltimore, MD
Purpose: Monotherapy using αCD28 or αCD40 antibodies significantly prolongs graft survival but does not induce tolerance in non-human primates (NHP). Here, we evaluate the relative…
2017 American Transplant Congress
Ex vivo Expanded Regulatory T cells Combined with Short-Term Costimulation Blockade Prevent Rejection of Vascularized Composite Allografts.
B. Oh, G. Furtmüller, M. Iglesias, M. Fryer, P. Akre, D. Cooney, W. Lee, G. Raimondi, G. Brandacher.
Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD
[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.…
2017 American Transplant Congress
Dual Costimulatory Blockades Failed to Achieve Transplant Tolerance Despite Induction of Mixed Chimerism in NHPs.
T. Oura,¹ K. Hotta,¹ I. Rosales,² A. Dehnadi,¹ J. Lei,¹ J. James Markmann,¹ M. Matsunami,¹ J. Paster,¹ I. Hanekamp,¹ K. Pruner,¹ K. Kawai,¹ D. Ndishabandi,² R.-N. Smith,² B. Cosimi,¹ T. Kawai.¹
¹Department of Surgery, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA; ²Department of Pathology, Massachusetts General Hospital, Boston, MA
Background: Our previous studies showed that substantial deletion of CD8+ memory T cells (TMEM) was necessary to induce mixed chimerism (MC) and allograft tolerance when…
2017 American Transplant Congress
Chimerism-Related Allotolerance Is Induced by Exosome Acquisition and Reprogramming of Host Dendritic Cells.
D. Lema,¹ W. Bracamonte-Baran,² E. Jankowska-Gan,¹ F. Claas,³ J. van Rood,³ A. Mulder,³ W. Burlingham.¹
¹Surgery - Transplant Division, University of Wisconsin-Madison, Madison, WI; ²Pathology, Division of Immunology, Johns Hopkins University, Baltimore, MD; ³Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands
Maternal microchimerism (MMc) has been associated with allo-specific graft tolerance in mice and humans. This tolerance is associated with membrane allo-antigen acquisition (mAAQ), which is…