Articles tagged "Rapamycin"

2019 American Transplant Congress
TORC1 Inhibition In Vitro and in a Humanized Mouse Model Protects Activated Human Regulatory T Cells from Self-Inflicted Damage via Granzyme B
B. S. Al Dulaijan, S. K. Eskandari, S. Cai, J. Y. Choi, H. Allos, I. Sulkaj, A. Bano, E. Al-Hussein, J. Azzi
Transplantation Research Center, BWH/Harvard Medical School, Boston, MA
*Purpose: Optimizing Regulatory T cells (Tregs) survival is of utmost importance to maximize the efficacy of utilizing them in adoptive cell therapy. We previously described…
2019 American Transplant Congress
Inhibition of mTORC2 Causes Hyper Phosphorylation of ERK Induced by Co-Ligation of HLA-I and II Antibody
Y. Jin¹, J. Sinnet-Smith², E. Rozengurt², E. F. Reed¹
¹Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA, ²Medicine, University of California Los Angeles, Los Angeles, CA
*Purpose: Transplant recipients developing donor specific antibodies (DSA) are at risk for antibody-mediated rejection (AMR). It has been reported that as many as 30% of…
2019 American Transplant Congress
Allogenic Islets Cure Diabetes Following Transplantation in Omental Pouch in a Non-Human Primate Model
J. Lei¹, H. Deng¹, K. Lee¹, C. Peters¹, G. Rickert¹, R. Ivy¹, M. Coronel², E. Yolcu³, H. Shirwan⁴, A. García⁵, J. Markmann¹
¹Surgery, Massachusetts General Hospital, Boston, MA, ²Surgery, Georgia Institute of Technology, Atlanta, GA, ³Institute for Cellular Therapeutics, University of Louisville School of Medicine, louisville, KY, ⁴Department of Microbiology and Immunology, University of Louisville School of Medicine, louisville, KY, ⁵School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA
*Purpose: In the current standard clinical transplant approach, islet cells are administered intravenously into the portal system where they lodge in the liver. This approach…
2019 American Transplant Congress
Use of mTOR Inhibitors in Hypersensitized Kidney Transplant Recipients: Breaking False Myths
D. Cucchiari¹, A. Molina-Andujar¹, E. Montagud-Marrahi¹, F. J. Centellas-Pérez², I. Revuelta¹, F. Oppenheimer¹, F. Diekmann¹
¹Renal Transplant Unit, Hospital Clínic, Barcelona, Spain, ²Complejo Hospitalario Universitario, Albacete, Spain
*Purpose: Many centers avoid the use of mTOR inhibitors (mTORi) in hypersensitized kidney transplant recipients and usually employ an immunosuppression based on Mycophenolic Acid (MPA),…
2018 American Transplant Congress
Glycolytic Bias in mTORC2-Deficient Dendritic Cells Potentiates Antigen-Specific Immunity and Accelerates Graft Rejection
A. Watson,¹ H. Dai,¹ J. Diaz-Perez,² A. Menk,³ M. Killeen,² G. Delgoffe,³ A. Mathers,² A. Thomson.¹
¹Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA; ²Dermatology, University of Pittsburgh, Pittsburgh, PA; ³Cancer Institute, University of Pittsburgh, Pittsburgh, PA.
The mechanistic target of rapamycin (mTOR) is known to function in two complexes: mTOR complex 1 (mTORC1) and mTORC2. While the function of mTORC1 in…
2018 American Transplant Congress
Rapamycin Impairs Human Endothelial Cell Alloimmunogenicity Independent of PD-1/PD-1 Ligand Inhibitory Signaling
Q. Gao, V. Bendersky, A. Kirk, H. Xu.
Department of Surgery, Duke University Medical Center, Durham, NC.
Rapamycin prevents costimulation blockade (CoB)-resistant rejection in mice and primates, and early human data suggests a similar salutary effect. We have hypothesized that one mechanism…
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
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
TORC1 Inhibition Protects Activated Human Regulatory T Cells from Self-Inflicted Damage via Granzyme B
B. Al Dulaijan, S. Eskandari, J. Karnyski, J. Assaker, S. Cai, A. Mansouri, M. Mohamed, J. Azzi.
Transplantation Research Center, BWH, Harvard Medical School, Boston, MA.
The safety and efficacy of adoptive transfer of regulatory T cells (Tregs) are being extensively investigated in ongoing clinical trials. However, these trials have been…
2018 American Transplant Congress
Lymph Node Reprogramming: Microparticle Delivery of Immune Signals to Induce Tolerance and Prolong Allograft Survival
Y. Xiong,¹ L. Tostanoski,² C. Jewell,² J. Bromberg.¹
¹UMB, MD; ²UMCP, MD.
Introduction: Microparticle (MP) loaded with peptide antigen plus other immune signals and delivered directly into lymph nodes (LN) can result in either pro-inflammatory or anti-inflammatory…