Bone marrow purging studies in acute myelogenous leukemia using the recombinant anti-CD33 immunotoxin HuM195/rGel Hatice Duzkale, Lance C Pagliaro, Michael.

Slides:

Advertisements

Similar presentations

Erik Ames, Salif Harouna, Colin Meyer, Lisbeth A. Welniak, William J

Advertisements

BCR-ABL nuclear entrapment kills human CML cells: ex vivo study on 35 patients with the combination of imatinib mesylate and leptomycin B by Alessandra.

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

High-Risk Acute Lymphoblastic Leukemia Cells with bcr-abl and Ink4a/Arf Mutations Retain Susceptibility to Alloreactive T Cells Faith M. Young, Andrew.

Outcomes of adults with acute myelogenous leukemia in remission given 550 cGy of single-exposure total body irradiation, cyclophosphamide, and unrelated.

Building better therapy for children with acute lymphoblastic leukemia

Rabbit Anti T-Lymphocyte Globulin Induces Apoptosis in Peripheral Blood Mononuclear Cell Compartments and Leukemia Cells, While Hematopoetic Stem Cells.

by JoAnn Castelli, Elaine K

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

Michael A. Pulsipher, Christina Peters, Ching-Hon Pui

Krystel Vincent, Marie-Pierre Hardy, Assya Trofimov, Céline M

Leukemia initiated by PMLRARα: the PML domain plays a critical role while retinoic acid–mediated transactivation is dispensable by Scott C. Kogan, Suk-hyun.

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

Chronic graft-versus-host disease after granulocyte colony-stimulating factor-mobilized allogeneic stem cell transplantation: the role of donor T-cell.

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

LBH589 Enhances T Cell Activation In Vivo and Accelerates Graft-versus-Host Disease in Mice Dapeng Wang, Cristina Iclozan, Chen Liu, Changqing Xia, Claudio.

Volume 123, Issue 1, Pages (July 2002)

Preactivation with IL-12, IL-15, and IL-18 Induces CD25 and a Functional High-Affinity IL-2 Receptor on Human Cytokine-Induced Memory-like Natural Killer.

Selective Ablation of Acute Myeloid Leukemia Using Antibody-Targeted Chemotherapy: A Phase I Study of an Anti-CD33 Calicheamicin Immunoconjugate by E.L.

Volume 14, Issue 3, Pages (September 2008)

Lack of the adhesion molecules P-selectin and intercellular adhesion molecule-1 accelerate the development of BCR/ABL-induced chronic myeloid leukemia-like.

Results of minimally toxic nonmyeloablative transplantation in patients with sickle cell anemia and β-thalassemia Robert Iannone, James F Casella, Ephraim.

Combined CD4+ Donor Lymphocyte Infusion and Low-Dose Recombinant IL-2 Expand FOXP3+ Regulatory T Cells following Allogeneic Hematopoietic Stem Cell Transplantation

Low c-Kit Expression Level Induced by Stem Cell Factor Does Not Compromise Transplantation of Hematopoietic Stem Cells Chia-Ling Chen, Katerina Faltusova,

FLT3 ligand administration after hematopoietic cell transplantation increases circulating dendritic cell precursors that can be activated by CpG oligodeoxynucleotides.

Spontaneous Autologous Graft-versus-Host Disease in Plasma Cell Myeloma Autograft Recipients: Flow Cytometric Analysis of Hematopoietic Progenitor Cell.

Donor T Cells Administered Over HLA Class II Barriers Mediate Antitumor Immunity without Broad Off-Target Toxicity in a NOD/Scid Mouse Model of Acute.

Small-molecule XIAP inhibitors derepress downstream effector caspases and induce apoptosis of acute myeloid leukemia cells by Bing Z. Carter, Marcela Gronda,

Generation of Highly Cytotoxic Natural Killer Cells for Treatment of Acute Myelogenous Leukemia Using a Feeder-Free, Particle-Based Approach Jeremiah.

A Phase II Multicenter Study of Visilizumab, Humanized Anti-CD3 Antibody, to Treat Steroid-Refractory Acute Graft-versus-Host Disease Paul A. Carpenter,

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

Synergistic Cytotoxicity of Sorafenib with Busulfan and Nucleoside Analogs in Human FMS-like Tyrosine Kinase 3 Internal Tandem Duplications–Positive Acute.

Onset of thymic recovery and plateau of thymic output are differentially regulated after stem cell transplantation in children Matthias Eyrich, Gernot.

Enhanced antimicrobial activity of peptide-cocktails against common bacterial contaminants of ex vivo stored platelets K.V.K. Mohan, S. Sainath Rao,

Selective Purging of Human Multiple Myeloma Cells from Autologous Stem Cell Transplantation Grafts using Oncolytic Myxoma Virus Eric Bartee, Winnie M.

Minor histocompatibility antigen-specific cytotoxic T lymphocytes generated with dendritic cells from DLA-identical littermates George E. Georges, Marina.

Volume 23, Issue 3, Pages (March 2013)

Dinty J. Musk, David A. Banko, Paul J. Hergenrother

Expansion and Homing of Adoptively Transferred Human Natural Killer Cells in Immunodeficient Mice Varies with Product Preparation and In Vivo Cytokine.

Phase I/II Study of Intravenous Plerixafor Added to a Mobilization Regimen of Granulocyte Colony–Stimulating Factor in Lymphoma Patients Undergoing Autologous.

T Cell–Mediated Rejection of Human CD34+ Cells Is Prevented by Costimulatory Blockade in a Xenograft Model Annie L. Oh, Dolores Mahmud, Benedetta Nicolini,

Lymphocyte Subset Recovery and Outcome after Autologous Hematopoietic Stem Cell Transplantation for Plasma Cell Myeloma Jessica Rueff, Michael Medinger,

Natural Killer Cell Killing of Acute Myelogenous Leukemia and Acute Lymphoblastic Leukemia Blasts by Killer Cell Immunoglobulin-Like Receptor–Negative.

Volume 23, Issue 4, Pages (April 2015)

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

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

The TWEAK Receptor Fn14 Is a Therapeutic Target in Melanoma: Immunotoxins Targeting Fn14 Receptor for Malignant Melanoma Treatment Hong Zhou, Suhendan.

High Disease Burden Is Associated with Poor Outcomes for Patients with Acute Myeloid Leukemia Not in Remission Who Undergo Unrelated Donor Cell Transplantation

Amotosalen-treated donor T cells have polyclonal antigen-specific long-term function without graft-versus-host disease after allogeneic bone marrow transplantation

In Situ Activation and Expansion of Host Tregs: A New Approach to Enhance Donor Chimerism and Stable Engraftment in Major Histocompatibility Complex-Matched.

Heterogeneous Clearance of Antithymocyte Globulin after CD34+-Selected Allogeneic Hematopoietic Progenitor Cell Transplantation Irina Kakhniashvili,

B Cells and Transplantation: An Educational Resource

A Novel Soluble Form of Tim-3 Associated with Severe Graft-versus-Host Disease John A. Hansen, Samir M. Hanash, Laura Tabellini, Chris Baik, Richard L.

Efficacy of CD34+ Stem Cell Dose in Patients Undergoing Allogeneic Peripheral Blood Stem Cell Transplantation after Total Body Irradiation Anurag K.

CD25 expression distinguishes functionally distinct alloreactive CD4+ CD134+ (OX40+) T-cell subsets in acute graft-versus-host disease Philip R Streeter,

Response of Steroid-Refractory Acute GVHD to α1-Antitrypsin

Donor antigen-presenting cells regulate T-cell expansion and antitumor activity after allogeneic bone marrow transplantation Jian-Ming Li, Edmund K.

Volume 5, Issue 1, Pages (July 2009)

Volume 25, Issue 4, Pages (April 2014)

What is quality in a transplant program?

Rituximab Administration within 6 Months of T Cell-Depleted Allogeneic SCT is Associated with Prolonged Life-Threatening Cytopenias Zachariah McIver,

Decreased Serum Albumin as a Biomarker for Severe Acute Graft-versus-Host Disease after Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation

Allogeneic Hematopoietic Stem Cell Transplantation in FLT3-ITD–Positive Acute Myelogenous Leukemia: The Role for FLT3 Tyrosine Kinase Inhibitors Post-

Sarbjit S. Saini, MDa, Jennifer J

Volume 14, Issue 3, Pages (September 2008)

A Phase I Study in Adults of Clofarabine Combined with High-Dose Melphalan as Reduced-Intensity Conditioning for Allogeneic Transplantation Mark H. Kirschbaum,

Mary Eapen Biology of Blood and Marrow Transplantation

Volume 24, Issue 9, Pages (September 2016)

Optimal Donor Selection: Beyond HLA

Graft Monocytic Myeloid-Derived Suppressor Cell Content Predicts the Risk of Acute Graft-versus-Host Disease after Allogeneic Transplantation of Granulocyte.

Presentation transcript:

Bone marrow purging studies in acute myelogenous leukemia using the recombinant anti-CD33 immunotoxin HuM195/rGel Hatice Duzkale, Lance C Pagliaro, Michael G Rosenblum, Ali Varan, Baoshun Liu, James Reuben, William G Wierda, Martin Korbling, John D McMannis, Armand B Glassman, David A Scheinberg, Emil J Freireich Biology of Blood and Marrow Transplantation Volume 9, Issue 6, Pages 364-372 (June 2003) DOI: 10.1016/S1083-8791(03)00129-0

Figure 1 Time-course studies to determine optimal exposure duration and concentration of HuM195/rGel to provide maximal toxicity on HL60 cells. Log-phase cells were treated with various concentrations of HuM195/rGel and the cells were exposed for indicated times. After immunotoxin administration, cells were plated quadruplicate to determine colony number. Mean colony numbers are shown with 95% confidence intervals. Optimal exposure duration was approximately 24 hours and treatment with 5 to 10 nmol/L HuM195/rGel appeared to be a dose range for optimal biological effect. Biology of Blood and Marrow Transplantation 2003 9, 364-372DOI: (10.1016/S1083-8791(03)00129-0)

Figure 2 Internalization of HuM195/rGel on HL60 cells at various times as assessed by immunofluorescence microscopy. Cells were treated at various times with immunotoxin, washed and cell-surface bound immunotoxin was removed using an acid wash. The cells were then permeabilized and stained with anti-rGel polyclonal antibodies. As shown, cytosolic levels of the rGel toxin can be observed as early as 30 minutes after treatment. Fluorescence intensity and cell staining was maximal from 4 to 24 hours after treatment. Biology of Blood and Marrow Transplantation 2003 9, 364-372DOI: (10.1016/S1083-8791(03)00129-0)

Figure 3 Dose-response curve for a patient with accelerated-phase CML without (wo) or with (w) the F/T procedure. A leukemic blast isolate from a CML patient was treated with various concentrations of HuM195/rGel and subjected to freeze-thaw procedure (F/T). The number of colonies was then determined. As shown, the F/T procedure increased the cytotoxic effect of the immunotoxin by approximately 50% at all doses tested. Biology of Blood and Marrow Transplantation 2003 9, 364-372DOI: (10.1016/S1083-8791(03)00129-0)

Figure 4 Number of colonies formed by PBPCs treated with HuM195/rGel without (wo) or with (w) the F/T procedure. Each bar represents a median of 9 normal donor samples and includes standard error bars. As shown, the effect of the immunotoxin on normal donor colonies was minimal with or without subjecting cells to F/T. Biology of Blood and Marrow Transplantation 2003 9, 364-372DOI: (10.1016/S1083-8791(03)00129-0)

Figure 5 Solid bars represent absolute CD34-positive cell numbers under different treatment conditions using clinical scale procedures. Mean values (with standard error bars) from 10 PBPC samples are shown. PBPCs showed a reduction in number when subjected to F/T; however, treatment with the HuM195/rGel immunotoxin alone had no effect, nor did the immunotoxin increase the cell reduction caused by the F/T procedure. Biology of Blood and Marrow Transplantation 2003 9, 364-372DOI: (10.1016/S1083-8791(03)00129-0)

Figure 6 Colony formation of PBPCs from normal donors using clinical scale conditions. Mean values (with standard error bars) of 5 samples are shown. F/T, freeze/thaw; IT, immunotoxin. Biology of Blood and Marrow Transplantation 2003 9, 364-372DOI: (10.1016/S1083-8791(03)00129-0)

Figure 7 Number of colonies formed by HL60 cells after preparing a mixture of PBPCs and HL60 cells (at a 9:1 ratio) and treating with HuM195/rGel without (wo) or with (w) subsequent F/T procedure. Each bar represents a median (with standard error bars) of 9 normal donor samples mixed with HL60 cells. Colonies are formed only by HL60 cells. As this figure demonstrates, addition of as little as 1 nmol/L of the HuM195/rGel immunotoxin markedly impacts the HL60 colony number and combination of immunotoxin and F/T results in a 10-fold reduction in the colony-forming ability of HL60 cells. Biology of Blood and Marrow Transplantation 2003 9, 364-372DOI: (10.1016/S1083-8791(03)00129-0)