Adoptive Cellular Therapy using Cells Enriched for NKG2D+CD3+CD8+T Cells after Autologous Transplantation for Myeloma Kenneth R. Meehan, Laleh Talebian,

Slides:

Advertisements

Similar presentations

Supplementary Figure S1

Advertisements

Volume 143, Issue 2, Pages (February 2013)

Cytolytic effector mechanisms and gene expression in autologous graft-versus-host disease: distinct roles of perforin and Fas ligand Yuji Miura, Christopher.

Cytomegalovirus Viral Load and Virus-Specific Immune Reconstitution after Peripheral Blood Stem Cell versus Bone Marrow Transplantation Abraham Guerrero,

Role of Natural Killer Cells in Intravenous Immunoglobulin–Induced Graft-versus-Host Disease Inhibition in NOD/LtSz-scidIL2rg−/− (NSG) Mice Joëlle Gregoire-Gauthier,

In Vitro Evaluation of Graft-versus-Graft Alloreactivity as a Tool to Identify the Predominant Cord Blood Unit before Double Cord Blood Transplantation

How to Treat MDS without Stem Cell Transplantation

Expansion of NKG2A−LIR1− Natural Killer Cells in HLA-Matched, Killer Cell Immunoglobulin-Like Receptors/HLA-Ligand Mismatched Patients following Hematopoietic.

Suzanne L. Tomchuck, Wing H. Leung, Mari H. Dallas

Targeting CD138−/CD20+ Clonogenic Myeloma Precursor Cells Decreases These Cells and Induces Transferable Antimyeloma Immunity Lawrence G. Lum, Archana.

Ex vivo induction of multiple myeloma–specific cytotoxic T lymphocytes

Ex Vivo Rapamycin Generates Th1/Tc1 or Th2/Tc2 Effector T Cells With Enhanced In Vivo Function and Differential Sensitivity to Post-transplant Rapamycin.

Human Progenitor Cells Rapidly Mobilized by AMD3100 Repopulate NOD/SCID Mice with Increased Frequency in Comparison to Cells from the Same Donor Mobilized.

Volume 138, Issue 5, Pages e2 (May 2010)

Immune Tolerance to Self-Major Histocompatability Complex Class II Antigens after Bone Marrow Transplantation: Role of Regulatory T Cells Allan D. Hess,

Donor-Derived Natural Killer Cells Infused after Human Leukocyte Antigen– Haploidentical Hematopoietic Cell Transplantation: A Dose-Escalation Study Inpyo.

Up-regulation of NK Cell Activating Receptors Following Allogeneic Hematopoietic Stem Cell Transplantation under a Lymphodepleting Reduced Intensity Regimen.

Mycophenolic Acid Inhibits Natural Killer Cell Proliferation and Cytotoxic Function: A Possible Disadvantage of Including Mycophenolate Mofetil in the.

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

Elevated Numbers of Immature/Transitional CD21− B Lymphocytes and Deficiency of Memory CD27+ B Cells Identify Patients with Active Chronic Graft-versus-Host.

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

Cytomegalovirus-Specific Cytotoxic T Lymphocytes Can Be Efficiently Expanded from Granulocyte Colony-Stimulating Factor–Mobilized Hemopoietic Progenitor.

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

Volume 25, Issue 3, Pages (March 2017)

Adoptive Therapy with T Cells/NK Cells

Suppression of natural killer cells in the presence of CD34+ blood progenitor cells and peripheral blood lymphocytes J. Clausen, M. Enk, B. Vergeiner,

Combination Therapy Using IL-2 and Anti-CD25 Results in Augmented Natural Killer Cell–Mediated Antitumor Responses William H.D. Hallett, Erik Ames, Maite.

Homeostatic γδ T Cell Contents Are Preserved by Granulocyte Colony-Stimulating Factor Priming and Correlate with the Early Recovery of γδ T Cell Subsets.

Xinchun Chen, Yi Zeng, Gang Li, Nicolas Larmonier, Michael W

Partial T Cell-Depleted Allogeneic Stem Cell Transplantation following Reduced- Intensity Conditioning Creates a Platform for Immunotherapy with Donor.

Expansion of NKG2A−LIR1− Natural Killer Cells in HLA-Matched, Killer Cell Immunoglobulin-Like Receptors/HLA-Ligand Mismatched Patients following Hematopoietic.

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

Hydrodynamic Delivery of Human IL-15 cDNA Increases Murine Natural Killer Cell Recovery after Syngeneic Bone Marrow Transplantation Isabel Barao, Maite.

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.

Aging Impairs Long-Term Hematopoietic Regeneration after Autologous Stem Cell Transplantation Carolien M. Woolthuis, Niccoló Mariani, Rikst Nynke Verkaik-Schakel,

Treatment with Plerixafor in non-Hodgkin's Lymphoma and Multiple Myeloma Patients to Increase the Number of Peripheral Blood Stem Cells When Given a Mobilizing.

Claudio G. Brunstein, Bruce R. Blazar, Jeffrey S

New Light Chain Amyloid Response Criteria Help Risk Stratification of Patients by Day 100 after Autologous Hematopoietic Cell Transplantation Anita D'Souza,

Quantity and Quality Reconstitution of NKG2A+ Natural Killer Cells Are Associated with Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation

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.

Laurent Boissel, Hande H

Quantitation of Human Cells that Produce Neutrophils and Platelets in Vivo Obtained from Normal Donors Treated with Granulocyte Colony–Stimulating Factor.

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.

B Cells and Transplantation: An Educational Resource

Sarah A. Holstein, Paul G. Richardson, Jacob P. Laubach, Philip L

Kamal Kant Singh Abbi, Junting Zheng, Sean M

David J. Chung, MD, PhD, Katherine B. Pronschinske, Justin A

The Notch Ligands Jagged2, Delta1, and Delta4 Induce Differentiation and Expansion of Functional Human NK Cells from CD34+ Cord Blood Hematopoietic Progenitor.

Protective Immunity Transferred by Infusion of Cytomegalovirus-Specific CD8+ T Cells within Donor Grafts: Its Associations with Cytomegalovirus Reactivation.

Regression Models for Hazard Rates Versus Cumulative Incidence Probabilities in Hematopoietic Cell Transplantation Data Brent R. Logan, Mei-Jie Zhang,

Pauline Damien, David S. Allan

What is quality in a transplant program?

Issues of Aging and Geriatric Medicine: Relevance to Cancer Treatment and Hematopoietic Reconstitution William B. Ershler, Andrew S. Artz, Evan T. Keller

Robin L. Williams, Sarah Cooley, Veronika Bachanova, Bruce R

Cord Blood Nucleated Cells Induce Delayed T Cell Alloreactivity

Melissa A. Mazur, Craig C. Davis, Paul Szabolcs, MD

Blood and Marrow Transplant Handbook

Bernard Maybury, Gordon Cook, Guy Pratt, Kwee Yong, Karthik Ramasamy

Abnormalities of the Bone Marrow Immune Microenvironment in Patients with Prolonged Isolated Thrombocytopenia after Allogeneic Hematopoietic Stem Cell.

Mammen Chandy Biology of Blood and Marrow Transplantation

Adoptive Immunotherapy with Cytokine-Induced Killer Cells for Patients with Relapsed Hematologic Malignancies after Allogeneic Hematopoietic Cell Transplantation

Addition of Plerixafor to Mobilization Regimens in Autologous Peripheral Blood Stem Cell Transplants Does Not Affect the Correlation of Preharvest Hematopoietic.

Treatment versus Transplant for Challenging Hematologic Disorders

Early Recovery of CD4 T Cell Receptor Diversity after “Lymphoablative” Conditioning and Autologous CD34 Cell Transplantation Jan Storek, Zhao Zhao, Yiping.

Mary Eapen Biology of Blood and Marrow Transplantation

Immunologic and pharmacokinetic studies.

Disparities in Utilization of Autologous Hematopoietic Cell Transplantation for Treatment of Multiple Myeloma Luciano J. Costa, Jia-Xing Huang, Parameswaran.

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

Presentation transcript:

Adoptive Cellular Therapy using Cells Enriched for NKG2D+CD3+CD8+T Cells after Autologous Transplantation for Myeloma Kenneth R. Meehan, Laleh Talebian, Tor D. Tosteson, John M. Hill, Zbigniew Szczepiorkowski, Charles L. Sentman, Marc S. Ernstoff Biology of Blood and Marrow Transplantation Volume 19, Issue 1, Pages 129-137 (January 2013) DOI: 10.1016/j.bbmt.2012.08.018 Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 Treatment schema. HPC indicates hematopoietic progenitor cells. IL-2 was administered weeks 1 through 4. Week 1 = day #3 posttransplantation; week 2 = day #14 posttransplantation; week 4 = day #28 posttransplantation; and week 8 = day #56 posttransplantation. Biology of Blood and Marrow Transplantation 2013 19, 129-137DOI: (10.1016/j.bbmt.2012.08.018) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Patient accrual to trial. Demonstrates the patients' accrual to the trial and distribution into evaluable and nonevaluable groups. Biology of Blood and Marrow Transplantation 2013 19, 129-137DOI: (10.1016/j.bbmt.2012.08.018) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Lymphocyte recovery on day 15 after transplantation. (A) Absolute lymphocyte numbers were calculated for each patient based on the number of lymphocytes circulating on day 15 after transplantation (ALC15). When compared to the control group (n = 6), ALC15 in the study group (n = 17) is significantly increased (P < .04). The control group = patients not treated on trial; the study group = patients treated on trial. (B) Flow cytometry identified the number of NKG2D+CD3+CD8+ T cells circulating in the study group (n = 12) and the control group (n = 4) patients on day 15 after transplantation (P = .02). The control group = patients not treated on trial; the study group = patients treated on trial. (C) Blood samples were obtained from patients treated on the trial (study group; n = 7) and patients from the control group (n = 4) between days 21 and 28 after transplantation. Flow cytometric analyses identified cell populations circulating in the blood in the 2 groups. When comparing cellular subsets between the 2 groups, there was a statistically significant increase in CD3+ T cells (P < .0001), CD4+ T cells (P < .0009), CD8+ T cells (P < .007), and CD25+ cells (P < .009). The control group = patients not treated on trial; the study group = patients treated on trial. ∗ Defines statistically significant results. Biology of Blood and Marrow Transplantation 2013 19, 129-137DOI: (10.1016/j.bbmt.2012.08.018) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 Circulating lymphocyte subsets in peripheral blood after transplantation. Phenotypic analyses identified the absolute number of NKG2D+CCD3+CD8+ (A), CD3+CD8+ (B), CD3+CD8+CD56+ (C), and NKG2D+CD3-CD56+ cells/μL (D) in the study group (n = 12) and in the control group (n = 4) between days 21 and 28 after transplantation. There was an increase in the absolute number of circulating NKG2D+CD3+CD8+ T cells (P < .004), CD3+CD8+ T cells (P < .04), CD3+CD8+CD56+ (P < .004), and NKG2D+CD3-CD56+ cells (P < .003) when compared to circulating cells in the control group. ∗ Defines statistically significant results. Biology of Blood and Marrow Transplantation 2013 19, 129-137DOI: (10.1016/j.bbmt.2012.08.018) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 5 NKG2D ligand expression in autologous myeloma cells. NKG2D ligand expression on autologous myeloma cells (n = 5) or normal control marrows (n = 3) was measured by labeling cells with Abs directed against CD138, in combination with Abs directed against MICA, MICB, ULBP1, ULBP2, and ULBP3. The expression of MICA (A), ULBP1 (B), and ULBP3 (C) is significantly elevated on autologous myeloma cells (MM), when compared to controls (Control) (P < .0001 for each of the 3 ligands). Biology of Blood and Marrow Transplantation 2013 19, 129-137DOI: (10.1016/j.bbmt.2012.08.018) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 6 Cytotoxicity after transplantation. Peripheral blood mononuclear cells (PBMCs) were isolated from study group patients (n = 5) and control patients (n = 4) between days 21 and 28 after transplantation. PBMCs were used as effector cells in a 51Cr-release cytotoxicity assay against a myeloma cell line (RPMI8226; E:T 100:1 for experimental and control groups). Myeloma cell lysis was significantly increased against RPMI cells in the study patients when compared with control patients (P = .002). Biology of Blood and Marrow Transplantation 2013 19, 129-137DOI: (10.1016/j.bbmt.2012.08.018) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 7 Cytotoxicity against autologous cells. Patients' mobilized peripheral blood mononuclear cells (PBMCs) were isolated from study group patients (n = 4) on the day of collection (“pre-expansion”) and were expanded ex vivo using methods described within the article with IL-2 and OKT3 for 7 days (“post-expansion”). Both pre-expansion and post-expansion cells served as effector cells in a 51Cr-release cytotoxicity assay against autologous myeloma cells (E:T 50:1). Myeloma cell lysis was significantly increased against autologous myeloma cells after enrichment for NKG2D+CD3+CD8+ T cells (P = .02). Cytotoxicity was inhibited by NKG2D receptor blocking (P < .001) using the same effectors and targets. Biology of Blood and Marrow Transplantation 2013 19, 129-137DOI: (10.1016/j.bbmt.2012.08.018) Copyright © 2013 American Society for Blood and Marrow Transplantation Terms and Conditions