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

Slides:

Advertisements

Similar presentations

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

Advertisements

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.

Blood Dendritic Cells Suppress NK Cell Function and Increase the Risk of Leukemia Relapse after Hematopoietic Cell Transplantation Antonio Perez-Martinez,

Successful Remission Rates and Survival after Lymphodepleting Chemotherapy and Donor Lymphocyte Infusion for Relapsed Hematologic Malignancies Postallogeneic.

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

Immunotherapy for Pediatric Cancer

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

Ping Zhang, Jieying Wu, Divino Deoliveira, Nelson J. Chao, Benny J

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

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.

Loss of T Follicular Helper Cells in the Peripheral Blood of Patients with Chronic Graft- versus-Host Disease David A. Knorr, Hongbo Wang, Mukta Aurora,

Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer by Jeffrey S. Miller, Yvette Soignier, Angela.

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

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

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.

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

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

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.

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

Blood Dendritic Cells Suppress NK Cell Function and Increase the Risk of Leukemia Relapse after Hematopoietic Cell Transplantation Antonio Perez-Martinez,

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

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

Impact of Allele-Level HLA Mismatch on Outcomes in Recipients of Double Umbilical Cord Blood Transplantation Claudio G. Brunstein, Effie W. Petersdorf,

FTY720 Markedly Increases Alloengraftment but Does Not Eliminate Host Anti-Donor T Cells that Cause Graft Rejection on Its Withdrawal Patricia A. Taylor,

Volume 25, Issue 3, Pages (March 2017)

Adoptive Therapy with T Cells/NK Cells

Natural Killer Cell Differentiation from Hematopoietic Stem Cells: A Comparative Analysis of Heparin- and Stromal Cell–Supported Methods Steven A. Dezell,

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.

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.

The Pentostatin Plus Cyclophosphamide Nonmyeloablative Regimen Induces Durable Host T Cell Functional Deficits and Prevents Murine Marrow Allograft Rejection

Blocking Activator Protein 1 Activity in Donor Cells Reduces Severity of Acute Graft- Versus-Host Disease through Reciprocal Regulation of IL-17–Producing.

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

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

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

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

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

T Cell and B Cell Immunity can be Reconstituted with Mismatched Hematopoietic Stem Cell Transplantation Without Alkylator Therapy in Artemis-Deficient.

Claudio Brunstein, MD, PhD, Keli Hippen, Todd E

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

Effector Cells Derived from Host CD8 Memory T Cells Mediate Rapid Resistance against Minor Histocompatibility Antigen-Mismatched Allogeneic Marrow Grafts.

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.

Prevention of Graft-versus-Host Disease by Adoptive T Regulatory Therapy Is Associated with Active Repression of Peripheral Blood Toll-Like Receptor 5.

Elevation of Intracellular Cyclic AMP in Alloreactive CD4+ T Cells Induces Alloantigen- Specific Tolerance That Can Prevent GVHD Lethality In Vivo Matthew.

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.

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

Activated Notch Supports Development of Cytokine Producing NK Cells Which Are Hyporesponsive and Fail to Acquire NK Cell Effector Functions Veronika.

A comparison of gene transfer and antigen-loaded dendritic cells for the generation of CD4+ and CD8+ cytomegalovirus-specific T cells in HLA-A2+ and HLA-A2−

Reconstitution of Natural Killer Cell Receptor Repertoires after Unmanipulated HLA- Mismatched/Haploidentical Blood and Marrow Transplantation: Analyses.

Interleukin 17 Is Not Required for Autoimmune-Mediated Pathologic Damage during Chronic Graft-versus-Host Disease Xiao Chen, Rupali Das, Richard Komorowski,

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

Enhancing Trafficking of Adoptively Transferred Natural Killer Cells Via Prostaglandin E2 Signaling Folashade Otegbeye, MBChB MPH, Stephen Moreton, Evelyn.

Umbilical Cord Blood Xenografts in Immunodeficient Mice Reveal That T Cells Enhance Hematopoietic Engraftment Beyond Overcoming Immune Barriers by Stimulating.

CpG-Induced Myeloid CD11b+Gr-1+ Cells Efficiently Suppress T Cell–Mediated Immunoreactivity and Graft-Versus-Host Disease in a Murine Model of Allogeneic.

Adaptive Natural Killer Cell and Killer Cell Immunoglobulin–Like Receptor–Expressing T Cell Responses are Induced by Cytomegalovirus and Are Associated.

Cytokines and cytotoxic pathways in engraftment resistance to purified allogeneic hematopoietic stem cells Christian Scheffold, Yolanda C. Scheffold,

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

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

Cytokine-Induced Memory-Like Differentiation Enhances Unlicensed Natural Killer Cell Antileukemia and FcγRIIIa-Triggered Responses Julia A. Wagner, Melissa.

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

Richard Mitchell, John E. Wagner, Claudio Brunstein, Qing Cao, David H

Richard Mitchell, John E. Wagner, Claudio G

In Vivo Expansion of Regulatory T cells With IL-2/IL-2 mAb Complexes Prevents Anti- factor VIII Immune Responses in Hemophilia A Mice Treated With Factor.

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

Biology of Blood and Marrow Transplantation

Presentation transcript:

Expansion and Homing of Adoptively Transferred Human Natural Killer Cells in Immunodeficient Mice Varies with Product Preparation and In Vivo Cytokine Administration: Implications for Clinical Therapy Jeffrey S. Miller, Cliona M. Rooney, Julie Curtsinger, Ron McElmurry, Valarie McCullar, Michael R. Verneris, Natalia Lapteva, David McKenna, John E. Wagner, Bruce R. Blazar, Jakub Tolar Biology of Blood and Marrow Transplantation Volume 20, Issue 8, Pages 1252-1257 (August 2014) DOI: 10.1016/j.bbmt.2014.05.004 Copyright © 2014 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 GMP grade Ex-NK cells and FA-NK cells differ in phenotype and their ability to expand in mice in vivo. (A) The Ex-NK cell product contained an average of 88% NK cells, whereas the FA-NK cell product contained 40% NK cells after CD3 and CD19 depletion, with the remaining cells being CD14+ monocytes (not shown). Inset shows percent of Cr51-labeled K562 cells lysed when incubated for 4 hours with Ex-NK or FA-NK cells at the indicated ratios. (B) NSG mice were treated with 250 cGy and then Ex-NK or FA-NK cells (1 to 2 million absolute NK cells were held constant within each experiment) were infused i.v. Cytokines were administered after cell infusion as indicated. Blood was sampled weekly and tissues collected as indicated. (C) The number of human CD45+ NK cells in 100 μL of blood collected at the various times after transfer of Ex-NK or FA-NK cells obtained either directly from in vitro cultures (fresh) or thawed after cryopreservation in 10% DMSO (frozen). All mice were given IL-2 (6 doses, 5 μg/dose). Data are means ± SEM (n = 4). (D) The number of human CD45+ NK cells in 100 μL of blood collected at the indicated times after transfer of Ex-NK or FA-NK from fresh cultures. Mice were given cytokines as indicated; IL-2 was given in 6 doses of 10 μg/dose; IL-15 was given in 6 doses of 5 μg/dose. Data are means ± SEM (n = 6 to 16, depending on time point and group, as selected mice were killed 8 or 15 days after cell infusion). Biology of Blood and Marrow Transplantation 2014 20, 1252-1257DOI: (10.1016/j.bbmt.2014.05.004) Copyright © 2014 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Thawed GMP grade Ex-NK and FA-NK cells expand in vivo when cultured overnight with IL-2 before adoptive transfer. Ex-NK and FA-NK products were thawed after cryopreservation in 10% DMSO and transferred to NSG mice either immediately (Thaw/inject) or after overnight culture with IL-2 (O/N IL-2). All mice were subsequently given 6 doses of IL-15 at 5 μg/dose. (A) Cytotoxic activity of each product is shown as the percent of Cr51-labeled K562 cells lysed when incubated for 4 hours with each product at the indicated ratios. (B) The number of human CD45+ NK cells in 150 μL of blood collected on days 7 and 14 after transfer. Results shown are the means ± SEM, n = 6 mice per group. Biology of Blood and Marrow Transplantation 2014 20, 1252-1257DOI: (10.1016/j.bbmt.2014.05.004) Copyright © 2014 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Phenotype of GMP grade Ex-NK and FA-NK cells in the blood varies with NK cell source and cytokine conditions. Cells and mice were as described in Figure 1D. (A) Percent of human NK cells expressing any of 3 KIRs (CD158a, CD158b, or CD158e1). (B) Percent of human NK cells expressing NKG2A. (C) Percent of human NK cells expressing CD57. Results shown are the means ± SD (n = 7 to 16, depending on time point and group). Biology of Blood and Marrow Transplantation 2014 20, 1252-1257DOI: (10.1016/j.bbmt.2014.05.004) Copyright © 2014 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 GMP grade Ex-NK and FA-NK cells have different biodistribution in bone marrow and spleen. (A) The number of human NK cells in bone marrow and spleen of mice given Ex-NK or FA-NK cells and cytokines as shown in Figure 1B. (B) The percent of proliferating (as evidenced by coexpression of Ki-67 on CD56+/CD3- cells) human NK cells 8 days after adoptive transfer of Ex-NK or FA-NK cells in bone marrow or spleen, respectively. (C) The proportion of CD57+ human NK cells 8 (left) and 15 (right) days after adoptive transfer of Ex-NK or FA-NK cells in bone marrow or spleen, respectively. Data are mean ± SE for all analyses (n = 4). Where indicated, P values were determined using an unpaired t-test to compare results for bone marrow and spleen within a treatment group. Biology of Blood and Marrow Transplantation 2014 20, 1252-1257DOI: (10.1016/j.bbmt.2014.05.004) Copyright © 2014 American Society for Blood and Marrow Transplantation Terms and Conditions