Tolerance Induction Dr. S. Strober Stanford University.

Slides:

Advertisements

Similar presentations

Blood and marrow stem cell transplantation A.Basi ADULT HEMATOLOGIST,ONCOLOGIST IRAN UNIVERSITY OF MEDICAL SCIENCES.

Advertisements

Doug Brutlag 2011 Genomics, Bioinformatics & Medicine Doug Brutlag Professor Emeritus of.

Allogeneic Stem Cell Transplantation: The Journey

Tolerance Induction after Kidney Transplantation Stephan Busque MD M Sc FRCSC Director, Adult Kidney and Pancreas Transplantation Program Stanford University.

Graft vs Host Disease Remains the major cause of treatment related morbidity and mortality in allogeneic HCT. Caused by donor derived alloreactive T cells.

Blockade of osteopontin reduces alloreactive CD8 + T cell– mediated graft-versus-host disease by Fang Zhao, Yi Zhang, Hao Wang, Min Jin, Shan He, Yufang.

Total Body Irradiation Nancy J Tarbell, MD. Contents BMT Background/History TBI technique, dose rate and fractionation Acute Effects Late Effects References.

Allogeneic “Mini” Transplantation Mark B. Juckett M.D. June 4, 2004.

BENIN BLOOD & MARROW TRANSPLANT SOCIETY OF NIGERIA JULY STEM CELL TRANSPLANT CENTRE, BENIN Graft versus Host Disease in HSCT Anthony Oyekunle.

A classic case of loosing options… Hans H Hirsch Transplantation & Clinical Virology Department Biomedicine (Haus Petersplatz) Division Infection Diagnostics.

Total Body Irradiation Nancy J Tarbell, MD. Contents BMT Background/History TBI technique, dose rate and fractionation Acute Effects Late Effects References.

Hematopoietic Stem Cell Current Status and Future Directions

Haploidentical BMT with a Post-Infusion of Stem Cells Cyclophosphamide Approach is Feasible and Leads to a High Rate of Donor Engraftment in Haemoglobinopathies.

"Humanized Mouse model in biomedical science”

Heather J. Symons, Moshe Y

Induction of Graft-versus-Leukemia (GVL) Effect without Graft-versus-Host Disease (GVHD) by Pretransplant Donor Treatment with Immunomodulators Shoshana.

GVHD-Like Colitis in Renal Graft Recipient

Relationship between Mixed Chimerism and Clinical Tolerance after Combined Kidney and Hematopoietic Cell Transplantation using Total Lymphoid Irradiation.

Supplemental table 1 Patients' characteristics Variables Number

Joseph H. Chewning, Weiwei Zhang, David A. Randolph, C

Reduced Graft-versus-Host Disease in C3-Deficient Mice Is Associated with Decreased Donor Th1/Th17 Differentiation Qing Ma, Dan Li, Roza Nurieva, Rebecca.

Influence of Donor Microbiota on the Severity of Experimental Graft-versus-Host- Disease Isao Tawara, Chen Liu, Hiroya Tamaki, Tomomi Toubai, Yaping Sun,

IL-2–Targeted Therapy Ameliorates the Severity of Graft-versus-Host Disease: Ex Vivo Selective Depletion of Host-Reactive T Cells and In Vivo Therapy

Host conditioning with total lymphoid irradiation and antithymocyte globulin prevents graft-versus-host disease: the role of CD1-reactive natural killer.

Th2 Cell Therapy of Established Acute Graft-Versus-Host Disease Requires IL-4 and IL- 10 and Is Abrogated by IL-2 or Host-Type Antigen-Presenting Cells

Differential Effects of Gut-Homing Molecules CC Chemokine Receptor 9 and Integrin-β7 during Acute Graft-versus-Host Disease of the Liver Alina Schreder,

A New Strategy for Treatment of Autoimmune Diseases in Chimeric Resistant MRL/lpr Mice by Kenji Takeuchi, Muneo Inaba, Shigeo Miyashima, Ryokei Ogawa,

William H. D. Hallett, Weiqing Jing, William R. Drobyski, Bryon D

Hideki Nakasone, MD, PhD, David B

IL-21 blockade reduces graft-versus-host disease mortality by supporting inducible T regulatory cell generation by Christoph Bucher, Lisa Koch, Christine.

The histone methyltransferase Ezh2 is a crucial epigenetic regulator of allogeneic T-cell responses mediating graft-versus-host disease by Shan He, Fang.

Rare cells predict GVHD

Transplantation Rejection of foreign tissue grafts is due to immune responses to alloantigens on the graft Blood group antigens Polymorphic MHC antigens.

Blocking LFA-1 Activation with Lovastatin Prevents Graft-versus-Host Disease in Mouse Bone Marrow Transplantation Yang Wang, Dan Li, Dan Jones, Roland.

IL-17 Gene Ablation Does Not Impact Treg-Mediated Suppression of Graft-Versus-Host Disease after Bone Marrow Transplantation Lucrezia Colonna, Mareike.

Frequencies of immune cell types show much stronger variations between tumor types in the tumor infiltrate compared with the spleen and tumor-draining.

Treatment with a Rho Kinase Inhibitor Improves Survival from Graft-Versus-Host Disease in Mice after MHC-Haploidentical Hematopoietic Cell Transplantation

Pharmacologic Expansion of Donor-Derived, Naturally Occurring CD4+Foxp3+ Regulatory T Cells Reduces Acute Graft-versus-Host Disease Lethality Without.

Figure 2 Components of each transplantation platform

Immune tolerance induction by nonmyeloablative haploidentical HSCT combining T-cell depletion and posttransplant cyclophosphamide by Franco Aversa, Esther.

The Triterpenoid CDDO-Me Delays Murine Acute Graft-versus-Host Disease with the Preservation of Graft-versus-Tumor Effects after Allogeneic Bone Marrow.

Absence of donor Th17 leads to augmented Th1 differentiation and exacerbated acute graft-versus-host disease by Tangsheng Yi, Dongchang Zhao, Chia-Lei.

Inhibition of Cathepsin S Reduces Allogeneic T Cell Priming but Not Graft-versus-Host Disease Against Minor Histocompatibility Antigens Hisaki Fujii,

CD40 ligand-specific antibodies synergize with cyclophosphamide to promote long-term transplantation tolerance across MHC barriers but inhibit graft-vs-leukemia.

TIM-1 Blockade of the Donor Graft Provides Protection Against Lethal Gvhd Bettina P. Iliopoulou, PhD, Katie Hsu, MS, Antonio Pierini, MD, Gordon J. Freeman,

Essential Role of Interleukin-12/23p40 in the Development of Graft-versus-Host Disease in Mice Yongxia Wu, David Bastian, Steven Schutt, Hung Nguyen,

T helper17 Cells Are Sufficient But Not Necessary to Induce Acute Graft-Versus-Host Disease Cristina Iclozan, Yu Yu, Chen Liu, Yaming Liang, Tangsheng.

The Triterpenoid CDDO-Me Delays Murine Acute Graft-versus-Host Disease with the Preservation of Graft-versus-Tumor Effects after Allogeneic Bone Marrow.

PRO 140 Monoclonal Antibody to CCR5 Prevents Acute Xenogeneic Graft-versus-Host Disease in NOD-scid IL-2Rynull Mice Denis R. Burger, Yvonne Parker, Kathryn.

Host Basophils Are Dispensable for Induction of Donor T Helper 2 Cell Differentiation and Severity of Experimental Graft-versus-Host Disease Isao Tawara,

Th2 Cell Therapy of Established Acute Graft-Versus-Host Disease Requires IL-4 and IL- 10 and Is Abrogated by IL-2 or Host-Type Antigen-Presenting Cells

A Radio-Resistant Perforin-Expressing Lymphoid Population Controls Allogeneic T Cell Engraftment, Activation, and Onset of Graft-versus-Host Disease in.

Mammalian Target of Rapamycin Inhibitors Permit Regulatory T Cell Reconstitution and Inhibit Experimental Chronic Graft-versus-Host Disease Haruko Sugiyama,

A CD4 Domain 1 CC′ Loop Peptide Analogue Enhances Engraftment in a Murine Model of Bone Marrow Transplantation with Sublethal Conditioning Gabor Varadi,

Fig. 7. ApoMSCs exert immunosuppressive activity in GvHD and elicit IDO in engulfing recipient phagocytes. ApoMSCs exert immunosuppressive activity in.

Tracking ex vivo-expanded CD4+CD25+ and CD8+CD25+ regulatory T cells after infusion to prevent donor lymphocyte infusion-induced lethal acute graft-versus-host.

Recipient B Cells Are Not Required for Graft-Versus-Host Disease Induction Catherine Matte-Martone, Xiajian Wang, Britt Anderson, Dhanpat Jain, Anthony.

The Innate Immune Sensor Sting Can Augment or Ameliorate Graft-Versus-Host Disease Dependent on the Genetic Disparity between Donors and Recipients Cameron.

Brile Chung, Eric Dudl, Akira Toyama, Lora Barsky, Kenneth I. Weinberg

Targeting ST2 Alleviates Graft-Versus-Host Disease Mortality and Maintains Graft- Versus-Leukemia Jilu Zhang, PhD, Benjamin Ulrich, Abdulraouf Ramadan,

Importance of thymus to maintain operational tolerance to fully allogeneic cardiac grafts Masanori Niimi, MD, PhD, Nozomu Shirasugi, MD, Yosifumi Ikeda,

Addition of treosulfan to a nonmyeloablative conditioning regimen results in enhanced chimerism and immunologic tolerance in an experimental allogeneic.

Frédéric Baron, Rainer Storb

Induction of Lethal Graft-versus-Host Disease by Anti-CD137 Monoclonal Antibody in Mice Prone to Chronic Graft-versus-Host Disease Wonyoung Kim, Juyang.

Impact of prophylactic donor leukocyte infusions on mixed chimerism, graft-versus-host disease, and antitumor response in patients with advanced hematologic.

Inhibition of c-Rel Activity Prevents Graft-Versus-Host Disease without Compromising Tumor Immunity Yusuke Shono, Andrea Z. Tuckett, Hsiou-Chi Liou,

Roles of CD28, CTLA4, and Inducible Costimulator in Acute Graft-versus-Host Disease in Mice Jun Li, Kenrick Semple, Woong-Kyung Suh, Chen Liu, Fangping.

IL-17A mediates cutaneous GVHD

Anti-PD-1H Antibody Prevents Graft Versus Host Disease

Anti-Flk-1 treatment inhibits growth of s. c. 4T1 and B16 tumors. s. c

Presentation transcript:

Tolerance Induction Dr. S. Strober Stanford University

Holy Grails Graft Anti- Tumor Activity without Graft vs Host Disease after Bone Marrow Transplantation for Leukemia/Lymphoma Organ Transplant Acceptance without Mainteneance Immunosuppressive Drugs(Immune Tolerance)

Total Lymphoid Irradiation Treatment for Hodgkin’s Disease Safe and effective (10,000 patients ) Multiple small doses of irradiation Targeted to lymph nodes, spleen, and thymus-other tissues shielded Outpatient procedure

Non-Myeloablative TLI/ATS Protocol ATS i.p. Injections D-24 D-12 D-10 D-8 D-1 D0 Donor: C57BL/6 (H2b) Bone marrow + or - Spleen or blood T cells Recipient: BALB/c Total Lymphoid Irradiation:17 Doses (240 cGy/dose) *Figure by A. Pillai MD

TLI + ATG Treated Mice are Resistant to GVHD Lan F. et al., J. Immunol. 167, 2001

TLI/ATG Conditioning for Hematolymphoid Malignancies Using MRD/URD ATG 1.5 mg/kg/day Day 0 GVHD prophylaxis Day 180 Days -11 to -7 CSA MMF TLI 800 cGy over 10 fractions Days -4 to -1Days -11 to -7 Infection Prophylaxis HSV: if +ve acyclovir 400 mg BID CMV: blood PCR weekly EBV: blood PCR every 2 weeks PCP: Septra DS BID weekends D+42 Fungus: if prior infection or URD Lowsky R, et al., NEJM Sept 2005

Sykes and Spitzer, Nat. Med.11,1164: 2005

Non-Myeloablative Post-Transplant Conditioning And Bone Marrow Cell Infusion Non-Myeloablative Post-Transplant Conditioning And Bone Marrow Cell Infusion ATG i.p. Injections D0 D1 D2 D4 D6 D8 D14 D15 Donor (C57BL/6) Bone marrow cell infusion (50 x 10 6 ) Heterotopic Heart TX Donor: C57BL/6 (neonatal) Recipient: BALB/c Total Lymphoid Irradiation:10 Doses (240 cGy/dose)

Heterotopic Heart Graft Survival Organ Donor: CD1d-/- (BALB/c background) or WT BALB/c Recipient: C57BL/6 BM Donor: CD1d-/- (BALB/c background) Or WT BALB/c