DOCSLIB.ORG

Tumor Effect

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Tumor Effect Biology of Blood and Marrow Transplantation 10:40-48 (2004) ᮊ 2004 American Society for Blood and Marrow Transplantation 1083-8791/04/1001-0004$30.00/0 doi:10.1016/j.bbmt.2003.09.013 Allogeneic versus Syngeneic Killer Splenocytes as Effector Cells for the Induction of Graft-versus- Tumor Effect Shoshana Morecki, Elena Yacovlev, Yael Gelfand, Anna Vilensky, Shimon Slavin Department of Bone Marrow Transplantation & Cancer Immunotherapy, Cell Therapy & Transplantation Research Center, Hadassah University Hospital, Jerusalem, Israel Correspondence and reprint requests: Shoshana Morecki, PhD, Department of BMT, Hadassah University Hospital, Jerusalem 91120, Israel (e-mail: [email protected]). Received August 8, 2003; accepted September 22, 2003 ABSTRACT The effect of allogeneic versus syngeneic killer cells derived from normal or severe combined immunodefi- ciency disease (SCID) mice was evaluated for induction of antitumor reaction in a murine model of mammary carcinoma. Tumor cells of H-2d origin were injected intravenously into H-2d/b mice 24 hours after total body irradiation (4 Gy). On the following day, lymphokine-activated killer (LAK) splenocytes, derived from either minor (H-2d) or major (H-2b) histocompatibility complex (MHC)–mismatched parental normal mice or MHC (H-2b)–mismatched SCID mice, were given intravenously. LAK cells of H-2d normal or SCID mice, syngeneic to the tumor, were inoculated in parallel. The results show that LAK cells derived from minor histocompat- ibility complex–mismatched or MHC-mismatched parental normal mice improved the probability of tumor- free survival as compared with LAK cells syngeneic to the tumor cells, but they aggravated the severity of graft-versus-host disease. SCID splenocytes serving as a source of natural killer (NK) cells were expanded and activated in vitro by rIL-2 to obtain a sufficient number of DX5؉ CD3؊ CD8؊ NK cells (SCID-LAK). H-2b SCID-LAK cells did not cause graft-versus-host disease and significantly delayed tumor growth compared with syngeneic H-2d SCID-LAK cells, as indicated by tumor colony assays in vitro and adoptive transfer experi- ments. However, the graft-versus-tumor effect was not long lasting, and treated mice finally died of tumor. Our results show an advantage of allogeneic over syngeneic cell therapy for achieving a graft-versus-tumor effect by rIL-2–activated T cells and NK cells. Periodic repetition of NK treatments may be required to achieve more durable antitumor effects. © 2004 American Society for Blood and Marrow Transplantation KEY WORDS Allogeneic killer cells ● Syngeneic killer cells ● SCID mice ● Graft-versus-tumor effect INTRODUCTION disease (GVHD) [12]. Furthermore, donor lympho- cyte infusion given after HSCT was shown to play a Immunotherapy strategies that aim to amplify an key role in eradicating malignant cells and preventing immune response and break tolerance to the tumor relapse [3-6,13-15]. The antitumor effects of alloreac- cells are mostly based on the use of tumor-syngeneic/ tive donor lymphocytes, designated as GVL and graft- autologous effector cells in both experimental models versus-tumor (GVT) effects, were ascribed mainly to and cancer patients [1-11]. During the last decade, an allogeneic T lymphocytes that recognize malignant increasing number of protocols based on an allogeneic cells in a major histocompatibility complex (MHC)– reaction between immunocompetent effector cells and restricted fashion and to MHC-nonrestricted natural tumor target cells were developed. This strategy killer (NK) and lymphokine-activated killer (LAK) emerged from clinical observations after allogeneic cells [16-20]. Unlike T cells, which are activated hematopoietic stem cell transplantation (HSCT), through recognition of foreign epitopes, it is sug- where there seemed to be a correlation between graft- gested that NK-cell activation is mediated via MHC versus-leukemia (GVL) effects and graft-versus-host class I missing-self epitopes when the negative signals 40 Allogeneic Killer Cells for Cancer of killing-inhibitory receptors (KIR) on the NK cells lands) in culture medium of 4T1 supplemented with Ϫ cannot be neutralized [21-23]. Allogeneic cell therapy 2-mercaptoethanol (5 ϫ 10 5 mol/L) and sodium (alloCT) has pronounced antitumor effects but is of- pyruvate (1 mmol/L; complete LAK medium). After 4 ten complicated by the development of GVHD, which days in a CO2 incubator at 37°C, cells were washed ϩ is ascribed to immunocompetent donor CD4 and and tested for their ability to exert an antitumor re- ϩ CD8 T cells that target organs such as skin, gut, sponse in vivo. liver, and lung [24-27]. In contrast to T cells, alloge- neic NK cells can mediate antitumor responses with- Propagation of LAK SCID Cells out causing GVHD when administered to immuno- Single-cell suspensions of splenocytes and bone compromised mice or humans [17-20], thus marrow (BM) cells derived from SCID mice were suggesting that NK alloreactivity warrants further prepared in complete LAK medium supplemented study as a potentially safer antitumor modality. with 10 ␮g/mL indomethacin (Sigma, St. Louis, MO). Encouraged by the efficient antitumor effects of Cell suspensions at a concentration of 1 ϫ 106/mL alloCT in previous studies, yet aware of the associated were plated in 6-well tissue culture plates (Corning, complications, we compared the efficacy of allogeneic New York, NY) or tissue culture flasks containing versus syngeneic cell therapy (synCT) by using various 3000 IU/mL rIL-2, according to the total number of sources of lymphokine-activated T and NK cells in an cells obtained. Cell and rIL-2 concentrations were attempt to induce GVT effects in a murine model of adjusted with fresh complete medium to 1 ϫ 106/mL mammary carcinoma. and 3000 IU/mL, respectively, every 3 to 4 days. Flow Cytometry Analysis MATERIALS AND METHODS Peripheral blood mononuclear cells (5 ϫ 105) Mice were stained directly with phycoerythrin anti-mouse ϩ BALB/c (H-2d) (BALB), C57BL/6 (H-2b) (C57) Pan NK cells (DX5) to detect NK1.1 cells, fluores- d d/b DBA/2 (H-2 ) (BALB/cXC57BL/6) F1 (H-2 )(F1), cein isothiocyanate (FITC) anti-mouse CD3 (17A2), and C.B-17/IcrHsd-scid (H-2d; SCID, severe com- and FITC anti-mouse CD8a (53-6.7). Phycoerythrin bined immunodeficiency disease) (C.B-17) mice, aged rat immunoglobulin M isotype standard (R4-22) and 9 to 12 weeks, were obtained from Harlan Sprague FITC rat immunoglobulin G2b isotype standard Dawley (Indianapolis, IN). C57BL/6J-PrkdcϽscidϾ/ (A95-1) were used as isotype controls. All reagents SzJ (H-2b) (C57 SCID) mice were obtained from were purchased from BD PharMingen (San Diego, Jackson Laboratory (Bar Harbor, ME). All mice were CA). All samples were preincubated for 10 min on ice maintained in the Hadassah University Hospital in with unlabeled rat anti-mouse CD32/16 antibodies accordance with the national laws and regulations for (Southern Biotechnology Associates, Inc., Birming- the protection of animal welfare. ham, AL) to prevent nonspecific staining through the Fc fraction of the labeled antibodies. Staining was Tumor Cells performed as described previously [31]. 4T1 is a tumor cell line established from a cell 4T1 Clonogenic Assay subpopulation isolated from a single spontaneously arising mammary tumor in a BALB/c (H-2d) mouse Lung metastases were measured as already de- [28]. 4T1 cells were maintained in 10% fetal bovine scribed [32]. Briefly, lungs were harvested from 3 mice serum, 2 mmol/L glutamine streptomycin 100 ␮g/ of each experimental group 13 to 14 days after tumor mL, penicillin 100 U/mL, and 1% nonessential amino inoculation. Single-cell suspensions were prepared in acid (culture medium of 4TI) and prepared for intra- serial dilutions in culture medium of 4T1 including 60 venous (IV; 0.25 mL per mouse) and intradermal (0.1 ␮mol/L 2-amino-6 mercaptopurine (Sigma) and mL per mouse) inoculation or were prepared for in plated in 100 ϫ 20 mm tissue culture dishes (Becton vitro assays as described previously [29]. Yac-1 (H-2a) Dickinson Labware, Franklin Lakes, NJ). Tumor col- (Yac) is a cell line sensitive to the cytotoxic activity of onies were fixed and stained with 0.03% methylene NK cells [30] and acts as target cells in chromium 51 blue 10 to 14 days after plating. The number of tumor release assays. Cells were kept at 37°C in a humidified colonies was calculated per mouse lung for each ex- 5% CO2/air incubator. perimental group relative to 100% 4T1 colonies in the control group of untreated mice. Preparation of LAK Normal Splenocytes Measurement of Cytotoxic Activity Spleen cells (1 ϫ 106/mL) were plated in 225-cm2 tissue culture flasks (Costar, Cambridge, MA) con- Cells harvested from normal LAK and SCID- taining 6000 IU/mL recombinant interleukin (rIL)-2 LAK cultures were washed, diluted to 5 ϫ 106/mL, (Proleukin; Chiron BV, Amsterdam, The Nether- and tested in a standard 4-hour chromium 51 release BB&MT 41 S. Morecki et al. Table 1. Effects of Syngeneic versus Allogeneic Cell Therapy on Survival of Tumor-Inoculated Mice Cause of Death No. Disease- Survival,* Free Effector Cells Median (Range) No. Mice Tumor-Related GVHD-Related Survivors Tumor only 33 (20-137) 31 31 0 0 F1 splenocytes 33 (22-205)‡ 26 25 0 1 BALB splenocytes 28 (25-50) 24 24 0 0 C57 splenocytes 17 (13-20) 15 0 15 0 BALB LAK cells 33 (27-50) 18 18 0 0 DBA LAK cells† 41 (28-180)‡ 18 14 2 2 F1 LAK cells 38 (30-138)‡ 10 9 0 1 C57 LAK cells 18 (14-20) 10 0 10 0 ϫ ϫ 4 (BALB/c C57BL/6) F1 mice were inoculated with 5 10 4T1 cells 24 hours after receiving 4 Gy of total body irradiation. One day later, 20 to 25 ϫ 106 effector cells derived from normal mice were given to them intravenously, and rIL-2 was administered intraperitoneally for 3 consecutive days at 5 ϫ 104 IU/d, starting from the day of cell therapy.
Load more

Recommended publications
  • Special Report Second EBMT Workshop on Reduced Intensity Allogeneic Hemopoietic Stem Cell Transplants (RI-HSCT)
    Bone Marrow Transplantation (2002) 29, 191–195 2002 Nature Publishing Group All rights reserved 0268–3369/02 $25.00 www.nature.com/bmt Special report Second EBMT Workshop on reduced intensity allogeneic hemopoietic stem cell transplants (RI-HSCT) A Bacigalupo Divisione Ematologia II Ospedale San Martino, Genova, Italy Summary: from AMGEN Europe, held a Workshop in Zurich on allo- geneic transplantation following non-myeloablative con- A second meeting on reduced intensity allogeneic stem ditioning. Tentative conclusions drawn from the 1999 cell transplants (RI-HSCT) was convened in Zurich in EBMT/AMGEN Workshop were published (1) and were February 2001 and focused on transplant-related mor- as follows: tality (TRM) and graft-versus-host disease (GVHD). Retrospective and prospective studies from the EBMT, • The term ‘minitransplant’ is probably misleading and national groups and single institutions included over reduced intensity allogeneic hematopoietic stem cell 900 patients: the incidence of acute GVHD grade III– transplantation (RI-HSCT) is preferred. IV was 12% (1–17%), extensive chronic GVHD 42% • RI-HSCT is an experimental procedure. (25–51%) and TRM 20% (14–38%). Conditioning regi- • RI-HSCT involves the use of normal donors and ethical mens could be classified into four major groups based issues apply as with any allogeneic transplant. on (1) total body irradiation (TBI) 200 cGy, (2) busulfan • Donors should be carefully evaluated because their 8 mg/kg, (3) thiotepa 10 mg/kg, and (4) melphalan 140 (probable) older age exposes them to an increased risk mg/m2: most of these regimens are given in association of complications. with fludarabine in different doses and use mobilized • At present, RI-HSCT should be offered to patients who peripheral blood as a source of stem cells.
    [Show full text]
  • Reduced Intensity Conditioning Allogeneic Stem
    Brief Report Reduced intensity conditioning allogeneic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation Mohamad Mohty,1 Myriam Labopin,2 Reza Tabrizzi,3 Niklas Theorin,4 Axel A Fauser,5 Alessandro Rambaldi,6 Johan Maertens,7 Shimon Slavin,8 Ignazio Majolino,9 Arnon Nagler,10 Didier Blaise,11 and Vanderson Rocha2,12 on behalf of the Acute Leukemia Working Party 1Service d’Hématologie Clinique, CHU Hôtel Dieu, Université de Nantes, Nantes, France; 2European Group for Blood and Marrow Transplantation (EBMT), Acute Leukemia Working Party, Hopital Saint-Antoine, Assistance Publique des Hôpitaux de Paris and Université de Paris 6, Pierre et Marie Curie, Paris, France; 3Centre Hospitalo-Universitaire de Bordeaux, Hôpital Haut-Leveque, Pessac, France; 4University Hospital, Dept. of Hematology, Linköping, Sweden; 5Klinik fuer Knochenmarktransplantation und Haematologie/Onkologie, Idar-Oberstein, Germany; 6Ospedale Bergamo, Divisione di Ematologia, Bergamo, Italy; 7University Hospital Gasthuisberg, Dept. of Hematology, Leuven, Belgium; 8Hadassah University Hospital, Department of Bone Marrow Transplantation, Jerusalem, Israel; 9Ospedale S. Camillo-Forlanini, Dept. of Hematology and BMT, Rome, Italy; 10Tel-Aviv University, Chaim Sheba Medical Center, Tel-Hashomer, Israel; 11Unité de Transplantation et de Thérapie Cellulaire, Institut Paoli-Calmettes, Marseille, France and 12Department of Hematology, Hopital Saint-Louis, Assistance Publique Hopitaux de Paris, Paris, France Citation: Mohty M, Labopin M, Tabrizzi R, Theorin N, Fauser AA, Rambaldi A, Maertens J, Slavin S, Majolino I, Nagler A, Blaise S, and Rocha V on behalf of the Acute Leukemia Working Party. Reduced intensity conditioning allogeneic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation.
    [Show full text]
  • Induction of Early Post-Transplant Graft-Versus-Leukemia Effects
    Research Article Induction of Early Post-Transplant Graft-versus-Leukemia Effects Using Intentionally Mismatched Donor Lymphocytes and Elimination of Alloantigen-Primed Donor Lymphocytes for Prevention of Graft-versus-Host Disease Iris Yung, Lola Weiss, Ali Abdul-Hai, Judith Kasir, Shoshana Reich, and Shimon Slavin Department of Bone Marrow Transplantation and Cancer Immunotherapy, Cell Therapy and Transplantation Research Center, Hadassah University Hospital, Jerusalem, Israel Abstract Using NST, the primary goal is to achieve engraftment of donor Graft-versus-leukemia (GVL) effects can be induced in tolerant stem cells thus establishing host-versus-graft unresponsiveness, mixed chimeras prepared with nonmyeloablative conditioning. and consequently, durable engraftment of donor immune system GVL effects can be amplified by post-grafting donor lymphocyte cells (8–10). However, in the absence of T-cell depletion, severe infusion (DLI). Unfortunately, DLI is frequently associated with acute and especially extensive chronic graft-versus-host disease graft-versus-host disease (GVHD). We investigated the feasibil- (GVHD) caused by alloreactive T lymphocytes still remain major ity of induction of potent GVL effects by DLI using intentionally obstacles. Over the years, several approaches have been proposed mismatched lymphocytes followed by elimination of alloreac- to prevent or at least control GVHD. Slavin et al. (11–13) and Sykes tive donor T cells by cyclophosphamide for prevention of and Sachs (14, 15) have documented in preclinical animal models lethal GVHD following induction of very short yet most potent that establishing a state of mixed chimerism was associated with a reduced risk of GVHD. Slavin et al. (12) and Weiss et al. (16) GVL effects.
    [Show full text]
  • IL-2-Targeted Therapy Ameliorates the Severity of Graft
    BIOLOGY 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 Shai Yarkoni,1 Tatyana B. Prigozhina,2 Shimon Slavin,3 Nadir Askenasy4 T cell depletion prevents graft-versus-host disease (GVHD) but also removes T cell-mediated support of hematopoietic cell engraftment. A chimeric molecule composed of IL-2 and caspase-3 (IL2-cas) has been evaluated as a therapeutic modality for GVHD and selective ex vivo depletion of host-reactive T cells. IL2- cas does not affect hematopoietic cell engraftment and significantly reduces the clinical and histological severity of GVHD. Early administration of IL2-cas reduced the lethal outcome of haploidentical trans- 1 plants, and survivor mice displayed markedly elevated levels of X-linked forkhead/winged helix (FoxP3 ; 1 1 50%) and CD25 FoxP3 T cells (35%) in the lymph nodes. The chimeric molecule induces in vitro 1 2 1 1 apoptosis in both CD4 CD25 and CD4 CD25 subsets of lymphocytes from alloimmunized mice, and stimulates proliferation of cells with highest levels of CD25 expression. Adoptive transfer of IL2- cas–pretreated viable splenocytes into sublethally irradiated haploidentical recipients resulted in 60% survival after a lethal challenge with lipopolysaccharide, which is associated with elevated fractions of 1 CD25highFoxP3 T cells in the lymph nodes of survivors. These data demonstrate that ex vivo purging of host-presensitized lymphocytes is effectively achieved with IL2-cas, and that IL-2–targeted apoptotic therapy reduces GVHD severity in vivo. Both approaches promote survival in lethal models of haploident- ical GVHD.
    [Show full text]
  • NIH Public Access Author Manuscript Arch Neurol
    NIH Public Access Author Manuscript Arch Neurol. Author manuscript; available in PMC 2011 February 9. NIH-PA Author ManuscriptPublished NIH-PA Author Manuscript in final edited NIH-PA Author Manuscript form as: Arch Neurol. 2010 October ; 67(10): 1187±1194. doi:10.1001/archneurol.2010.248. Safety and Immunological Effects of Mesenchymal Stem Cell Transplantation in Patients With Multiple Sclerosis and Amyotrophic Lateral Sclerosis Dr. Dimitrios Karussis, MD, PhD, Dr. Clementine Karageorgiou, MD, Dr. Adi Vaknin- Dembinsky, MD, PhD, Dr. Basan Gowda-Kurkalli, PhD, Dr. John M. Gomori, MD, Mr. Ibrahim Kassis, MSc, Dr. Jeff W. M. Bulte, PhD, Dr. Panayiota Petrou, MD, Dr. Tamir Ben- Hur, MD, PhD, Dr. Oded Abramsky, MD, PhD, and Dr. Shimon Slavin, MD Department of Neurology, Laboratory of Neuroimmunology and Agnes Ginges Center for Neurogenetics and Multiple Sclerosis Center (Drs Karussis, Vaknin-Dembinsky, Petrou, Ben-Hur, and Abramsky and Mr Kassis), Department of Bone Marrow Transplantation (Drs Gowda-Kurkalli and Slavin), and Unit of Neuroradiology, Department of Radiology (Dr Gomori), Hadassah Hebrew University Hospital, Jerusalem, Israel; Department of Neurology, Gennimatas General Hospital, Athens, Greece (Dr Karageorgiou); and Russell H. Morgan Department of Radiology and Radiological Science, Department of Biomedical Engineering, and Department of Chemical and Biomolecular Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland (Dr Bulte) Abstract Objective—To evaluate the feasibility, safety, and immunological effects of intrathecal and intravenous administration of autologous mesenchymal stem cells (MSCs) (also called mesenchymal stromal cells) in patients with multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Design—A phase 1/2 open-safety clinical trial.
    [Show full text]
  • Immune Inhibition of Rat Gliomas by Subcutaneous Exposure to Unmodified Live Tumor Cells
    SPLIT IMMUNITY: IMMUNE INHIBITION OF RAT GLIOMAS BY SUBCUTANEOUS EXPOSURE TO UNMODIFIED LIVE TUMOR CELLS. Ilan Volovitz †,* , Yotvat Marmor *, Meir Azulay *, Arthur Machlenkin *, Ofir Goldberger * , Felix Mor *, Shimon Slavin ‡, Zvi Ram †, Irun R. Cohen *and Lea Eisenbach * † The Cancer Immunotherapy lab, the Dept. of Neurosurgery. The Tel-Aviv Sourasky Medical Center. * The Dept. of Immunology. The Weizmann Institute of Science. ‡ The International Center for Cell Therapy & Cancer Immunotherapy, The Tel-Aviv Medical Complex, Tel-Aviv. ABSTRACT Gliomas, which appear to grow uninhibited in the brain, almost never metastasize outside the CNS. The rare occurrences of extracranial metastasis are usually associated with an immune compromised status of the host. This observation raises the possibility that some gliomas might not grow outside the CNS due to an inherent immune response. We now report that the highly malignant F98 Fischer rat undifferentiated glioma, which grows aggressively in the brain, spontaneously regresses when injected live subcutaneously (sc). We found that this regression is immune-mediated and that it markedly enhances the survival, or cures rats challenged with the same tumor intracranially (ic) either before or after the sc live-cell inoculation. Adoptive transfer experiments showed the effect was immune-mediated, and that the CD8 T-cell fraction, which exhibited direct tumor cytotoxicity, was more effective than the CD4 T-cell fraction in mediating resistance to intracranial challenge of naïve rats. The results in the F98 model were corroborated also in the Lewis rat CNS-1 astrocytoma model. In both tumor models the unprecedented survival results using live-cell immunization were significantly better than those achieved using immunization with irradiated cells.
    [Show full text]
  • Induction of Early Post-Transplant Graft-Versus-Leukemia Effects Using Intentionally Mismatched Donor Lymphocytes and Eliminatio
    Research Article Induction of Early Post-Transplant Graft-versus-Leukemia Effects Using Intentionally Mismatched Donor Lymphocytes and Elimination of Alloantigen-Primed Donor Lymphocytes for Prevention of Graft-versus-Host Disease Iris Yung, Lola Weiss, Ali Abdul-Hai, Judith Kasir, Shoshana Reich, and Shimon Slavin Department of Bone Marrow Transplantation and Cancer Immunotherapy, Cell Therapy and Transplantation Research Center, Hadassah University Hospital, Jerusalem, Israel Abstract Using NST, the primary goal is to achieve engraftment of donor Graft-versus-leukemia (GVL) effects can be induced in tolerant stem cells thus establishing host-versus-graft unresponsiveness, mixed chimeras prepared with nonmyeloablative conditioning. and consequently, durable engraftment of donor immune system GVL effects can be amplified by post-grafting donor lymphocyte cells (8–10). However, in the absence of T-cell depletion, severe infusion (DLI). Unfortunately, DLI is frequently associated with acute and especially extensive chronic graft-versus-host disease graft-versus-host disease (GVHD). We investigated the feasibil- (GVHD) caused by alloreactive T lymphocytes still remain major ity of induction of potent GVL effects by DLI using intentionally obstacles. Over the years, several approaches have been proposed mismatched lymphocytes followed by elimination of alloreac- to prevent or at least control GVHD. Slavin et al. (11–13) and Sykes tive donor T cells by cyclophosphamide for prevention of and Sachs (14, 15) have documented in preclinical animal models lethal GVHD following induction of very short yet most potent that establishing a state of mixed chimerism was associated with a reduced risk of GVHD. Slavin et al. (12) and Weiss et al. (16) GVL effects.
    [Show full text]
  • The Second International Meeting on Allogeneic Transplantation in Solid Tumors
    Bone Marrow Transplantation (2006) 38, 527–537 & 2006 Nature Publishing Group All rights reserved 0268-3369/06 $30.00 www.nature.com/bmt MEETING REPORT The Second International Meeting on Allogeneic Transplantation in Solid Tumors M Bregni1, NT Ueno2 and R Childs3 1Oncology-Hematology-Bone Marrow Transplant Unit, Department of Oncology, Istituto Scientifico San Raffaele, San Raffaele Hospital, Milan, Italy; 2Department of Blood and Marrow Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA and 3NHLBI, National Institutes of Health, Bethesda, MD, USA In October 2005,the second international meeting on convened in Stresa (Italy) by Marco Bregni, Naoto Ueno, allogeneic transplantation in solid tumors was convened in and Richard Childs under the auspices of the European Stresa (Italy). The aim of this second meeting was to Group for Blood and Marrow Transplantation (EBMT) share clinical experiences of allografting in solid tumors, Solid Tumor Working Party. The first meeting took to discuss preclinical data on the mechanisms of graft- place in Milano, Italy, in June 2002, and was a chance versus-tumor (GVT) effect,and to review methods for for people involved to communicate and discuss initial more efficacious transplant approaches. On the first day, clinical and biological studies of reduced-intensity allo- the most recent results in cancer immunotherapy were grafting in solid tumors.1 The aim of this second meeting reviewed; head-to head comparisons of clinical results was to share experiences of allografting for solid tumors, achieved by standard therapy and by allografting in renal, update data accumulated in this field over the past 3 years, breast,and ovarian cancer were presented.
    [Show full text]
  • A Patient's Path Through the Maze of Stem Cell Transplantation
    CY OCA AW V A D R A D < > W O T R 20 10 I L D M M S U T E S M C E L L A PAtient’s PATH THROUGH THE MAZE OF STEM CELL TRANSPLANTATION AN INTRODUCTION TO THE STEM CELL The first true stem cell was discovered and named in 1908 by the Russian scientist, Alexander Maksimov, A CLOSER LOOK who found that certain cells could generate blood cells. In 1963, Canadian researchers Earnest McCullough and James Till described the self- renewing nature of transplanted mouse mesenchymal cells. In 1998, Dr. James Thomson and his colleagues from the University of Wisconsin - Madison announced the successful AT STEM CELLS, extraction of stem cells from human embryos in the laboratory. Enormous excitement surrounds these and related discoveries because stem cells have the potential to develop into many different cells, which means they can serve as an internal repair system. When a stem cell divides, it has the potential to either continue PROCEDURES, functioning as is or to become another type of cell with a more specialized function, such as muscle, red blood or brain cell. The most important characteristic of stem cells is their ability to renew, repair or replace worn out or damaged tissue. FACILITIES AND An Introduction to Stem Cells We are now in 2010, faced with a multitude of potential stem cell therapy opportunities for those with ALS and other debilitating diseases and injuries. As a result, an entirely new and complicated collection of terms has emerged in the process. The terminology includes embryonic, adult, fetal, mesenchymal, umbilical cord THE EMERGENCE blood, amniotic, olfactory ensheathing cells, autologous, allogeneic and a whole host of other substrata of OF ALS WORLDWIDE stem cells, enough to confuse any patient and possibly even some of the scientists.
    [Show full text]
  • New Jersey Commission on Cancer Research
    New Jersey Commission on Cancer Research 2000 Annual Report "Dedicated to Conquering Cancer Through Scientific Research" The Honorable Donald T. DiFrancesco Acting Governor Dear Governor DiFrancesco: As the newly elected Chairman of the New Jersey Commission on Cancer Research, I am honored to present to you the Commission's report for the Year 2000. Consistent with its legislative mandate, the Commission focused its efforts during the past year on basic research directed to increase our understanding of this disease and reduce morbidity and mortality related to the disease. Toward this goal, the Commission awarded twelve grants for basic, clinical, and psychosocial research,seven pre-doctoral and post-doctoral research fellowships, and fifteen summer research fellowships, designed to encourage college students to pursue careers in cancer research. This year, the Commission began a more formal tracking program for past award recipients, and we continue to find that their productivity supports our contention that the monies expended have been a superb investment in the future of New Jersey's research infrastructure and institutions of higher learning. Past investigators supported by the Commission have, in large part, remained within New Jersey, contributed to a significant increase in research dollars flowing into the State, and provided an invaluable resource to research, educational, and corporate entities. The Commission has long recognized that research carried out in a vacuum has reduced value, and in this regard, we continue to serve as a catalyst and supporter of educational and research meetings. This year, the International Conference on Advances in Cancer Immunology, the Annual Retreat on Cancer Research in New Jersey and the Conference on Cancer Survivorship Throughout the Life-span, brought together hundreds of consumers, educators and scientists, in an atmosphere conducive to networking and program development, and in a way designed to highlight New Jersey's strengths in these programs.
    [Show full text]
  • Immune Inhibition Of
    Split Immunity: Immune Inhibition of Rat Gliomas by Subcutaneous Exposure to Unmodified Live Tumor Cells This information is current as Ilan Volovitz, Yotvat Marmor, Meir Azulay, Arthur of February 27, 2013. Machlenkin, Ofir Goldberger, Felix Mor, Shimon Slavin, Zvi Ram, Irun R. Cohen and Lea Eisenbach Downloaded from J Immunol 2011; 187:5452-5462; Prepublished online 12 October 2011; doi: 10.4049/jimmunol.1003946 http://www.jimmunol.org/content/187/10/5452 http://jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2011/10/12/jimmunol.100394 Material 6.DC1.html References This article cites 56 articles, 13 of which you can access for free at: http://www.jimmunol.org/content/187/10/5452.full#ref-list-1 at Weizmann Institute of Science on February 27, 2013 Subscriptions Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscriptions Permissions Submit copyright permission requests at: http://www.aai.org/ji/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/cgi/alerts/etoc The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 9650 Rockville Pike, Bethesda, MD 20814-3994. Copyright © 2011 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Split Immunity: Immune Inhibition of Rat Gliomas by Subcutaneous Exposure to Unmodified Live Tumor Cells Ilan Volovitz,*,† Yotvat Marmor,* Meir Azulay,* Arthur Machlenkin,* Ofir Goldberger,* Felix Mor,* Shimon Slavin,‡ Zvi Ram,† Irun R. Cohen,* and Lea Eisenbach* Gliomas that grow uninhibited in the brain almost never metastasize outside the CNS.
    [Show full text]
  • Split Immunity: Immune Inhibition of Rat Gliomas by Subcutaneous Exposure to Unmodified Live Tumor Cells
    Split Immunity: Immune Inhibition of Rat Gliomas by Subcutaneous Exposure to Unmodified Live Tumor Cells This information is current as Ilan Volovitz, Yotvat Marmor, Meir Azulay, Arthur of September 27, 2021. Machlenkin, Ofir Goldberger, Felix Mor, Shimon Slavin, Zvi Ram, Irun R. Cohen and Lea Eisenbach J Immunol 2011; 187:5452-5462; Prepublished online 12 October 2011; doi: 10.4049/jimmunol.1003946 Downloaded from http://www.jimmunol.org/content/187/10/5452 Supplementary http://www.jimmunol.org/content/suppl/2011/10/12/jimmunol.100394 Material 6.DC1 http://www.jimmunol.org/ References This article cites 56 articles, 11 of which you can access for free at: http://www.jimmunol.org/content/187/10/5452.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on September 27, 2021 • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2011 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Split Immunity: Immune Inhibition of Rat Gliomas by Subcutaneous Exposure to Unmodified Live Tumor Cells Ilan Volovitz,*,† Yotvat Marmor,* Meir Azulay,* Arthur Machlenkin,* Ofir Goldberger,* Felix Mor,* Shimon Slavin,‡ Zvi Ram,† Irun R.
    [Show full text]