scholarly journals An update on GM-CSF and its potential role in melanoma management

2020 ◽  
Vol 7 (3) ◽  
pp. MMT49
Author(s):  
Robert O Dillman
Keyword(s):  
Dendritic Cells ◽  
Stem Cell ◽  
Randomized Trials ◽  
Potential Role ◽  
Ex Vivo ◽  
Vaccine Adjuvant ◽  
Talimogene Laherparepvec ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Melanoma Treatment

GM-CSF drives the differentiation of granulocytes and monocyte/macrophages from hematopoietic stem cell progenitors. It is required for differentiating monocytes into dendritic cells (DC). Although approved for recovery of granulocytes/monocytes in patients receiving chemotherapy, G-CSF is preferred. Enthusiasm for GM-CSF monotherapy as a melanoma treatment was dampened by two large randomized trials. Although GM-CSF has been injected into tumors for many years, the efficacy of this has not been tested. There is a strong rationale for GM-CSF as a vaccine adjuvant, but it appears of benefit only for strategies that directly involve DCs, such as intratumor talimogene laherparepvec and vaccines in which DCs are loaded with antigen ex vivo and injected admixed with GM-CSF.

Role of plasmacytoid dendritic cells in immunity and tolerance after allogeneic hematopoietic stem cell transplantation

2003 ◽  
Vol 11 (3-4) ◽  
pp. 345-356 ◽  
Author(s):  
Mario Arpinati ◽  
Gabriella Chirumbolo ◽  
Benedetta Urbini ◽  
Giulia Perrone ◽  
Damiano Rondelli ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Plasmacytoid Dendritic Cells ◽  
Hematopoietic Stem

scholarly journals Ex vivo expansion of human hematopoietic stem and progenitor cells

Blood ◽  
2011 ◽  
Vol 117 (23) ◽  
pp. 6083-6090 ◽  
Author(s):  
Ann Dahlberg ◽  
Colleen Delaney ◽  
Irwin D. Bernstein
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Notch Signaling ◽  
Progenitor Cells ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Hematopoietic Growth Factors ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells

AbstractDespite progress in our understanding of the growth factors that support the progressive maturation of the various cell lineages of the hematopoietic system, less is known about factors that govern the self-renewal of hematopoietic stem and progenitor cells (HSPCs), and our ability to expand human HSPC numbers ex vivo remains limited. Interest in stem cell expansion has been heightened by the increasing importance of HSCs in the treatment of both malignant and nonmalignant diseases, as well as their use in gene therapy. To date, most attempts to ex vivo expand HSPCs have used hematopoietic growth factors but have not achieved clinically relevant effects. More recent approaches, including our studies in which activation of the Notch signaling pathway has enabled a clinically relevant ex vivo expansion of HSPCs, have led to renewed interest in this arena. Here we briefly review early attempts at ex vivo expansion by cytokine stimulation followed by an examination of our studies investigating the role of Notch signaling in HSPC self-renewal. We will also review other recently developed approaches for ex vivo expansion, primarily focused on the more extensively studied cord blood–derived stem cell. Finally, we discuss some of the challenges still facing this field.

Autologous nonmyeloablative hematopoietic stem cell transplantation in patients with severe anti-TNF refractory Crohn disease: long-term follow-up

Blood ◽  
2010 ◽  
Vol 116 (26) ◽  
pp. 6123-6132 ◽  
Author(s):  
Richard K. Burt ◽  
Robert M. Craig ◽  
Francesca Milanetti ◽  
Kathleen Quigley ◽  
Paula Gozdziak ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Crohn Disease ◽  
Ex Vivo ◽  
Activity Index ◽  
Clinical Relapse ◽  
Hematopoietic Stem

Abstract We evaluated the safety and clinical outcome of autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) in patients with severe Crohn disease (CD) defined as a Crohn Disease Activity Index (CDAI) greater than 250, and/or Crohn Severity Index greater than 16 despite anti–tumor necrosis factor therapy. Stem cells were mobilized from the peripheral blood using cyclophosphamide (2.0 g/m2) and G-CSF (10 μg/kg/day), enriched ex vivo by CD34+ selection, and reinfused after immune suppressive conditioning with cyclophosphamide (200 mg/kg) and either equine antithymocyte globulin (ATG, 90 mg/kg) or rabbit ATG (6 mg/kg). Eighteen of 24 patients are 5 or more years after transplantation. All patients went into remission with a CDAI less than 150. The percentage of clinical relapse-free survival defined as the percent free of restarting CD medical therapy after transplantation is 91% at 1 year, 63% at 2 years, 57% at 3 years, 39% at 4 years, and 19% at 5 years. The percentage of patients in remission (CDAI < 150), steroid-free, or medication-free at any posttransplantation evaluation interval more than 5 years after transplantation has remained at or greater than 70%, 80%, and 60%, respectively. This trial was registered at www.clinicaltrials.gov as NCT0027853.

scholarly journals Eliminating SCID row: new approaches to SCID

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 475-480 ◽  
Author(s):  
Donald B. Kohn
Keyword(s):  
Gene Therapy ◽  
Stem Cell ◽  
Ex Vivo ◽  
Autologous Transplantation ◽  
Unrelated Donor ◽  
Primary Immune Deficiency ◽  
Gene Repair ◽  
Gene Correction ◽  
Hematopoietic Stem ◽  
New Approaches

Abstract Treatments for patients with SCID by hematopoietic stem cell transplantation (HSCT) have changed this otherwise lethal primary immune deficiency disorder into one with an increasingly good prognosis. SCID has been the paradigm disorder supporting many key advances in the field of HSCT, with first-in-human successes with matched sibling, haploidentical, and matched unrelated donor allogeneic transplantations. Nevertheless, the optimal approaches for HSCT are still being defined, including determining the optimal stem cell sources, the use and types of pretransplantation conditioning, and applications for SCID subtypes associated with radiosensitivity, for patients with active viral infections and for neonates. Alternatively, autologous transplantation after ex vivo gene correction (gene therapy) has been applied successfully to the treatment of adenosine deaminase–deficient SCID and X-linked SCID by vector-mediated gene addition. Gene therapy holds the prospect of avoiding risks of GVHD and would allow each patient to be their own donor. New approaches to gene therapy by gene correction in autologous HSCs using site-specific endonuclease-mediated homology-driven gene repair are under development. With newborn screening becoming more widely adopted to detect SCID patients before they develop complications, the prognosis for SCID is expected to improve further. This chapter reviews recent advances and ongoing controversies in allogeneic and autologous HSCT for SCID.

Expansion of human cord blood CD34+CD38−cells in ex vivo culture during retroviral transduction without a corresponding increase in SCID repopulating cell (SRC) frequency: dissociation of SRC phenotype and function

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 102-110 ◽  
Author(s):  
Craig Dorrell ◽  
Olga I. Gan ◽  
Daniel S. Pereira ◽  
Robert G. Hawley ◽  
John E. Dick
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cord Blood ◽  
Cell Function ◽  
Cultured Cells ◽  
Genetic Manipulation ◽  
Ex Vivo ◽  
Hematopoietic Stem ◽  
Retroviral Transduction ◽  
Large Expansion

Abstract Current procedures for the genetic manipulation of hematopoietic stem cells are relatively inefficient due, in part, to a poor understanding of the conditions for ex vivo maintenance or expansion of stem cells. We report improvements in the retroviral transduction of human stem cells based on the SCID-repopulating cell (SRC) assay and analysis of Lin− CD34+CD38−cells as a surrogate measure of stem cell function. Based on our earlier study of the conditions required for ex vivo expansion of Lin−CD34+ CD38− cells and SRC, CD34+–enriched lineage–depleted umbilical cord blood cells were cultured for 2 to 6 days on fibronectin fragment in MGIN (MSCV-EGFP-Neo) retroviral supernatant (containing 1.5% fetal bovine serum) and IL-6, SCF, Flt-3 ligand, and G-CSF. Both CD34+CD38− cells (20.8%) and CFC (26.3%) were efficiently marked. When the bone marrow of engrafted NOD/SCID mice was examined, 75% (12/16) contained multilineage (myeloid and B lymphoid) EGFP+ human cells composing as much as 59% of the graft. Half of these mice received a limiting dose of SRC, suggesting that the marked cells were derived from a single transduced SRC. Surprisingly, these culture conditions produced a large expansion (166-fold) of cells with the CD34+CD38− phenotype (n = 20). However, there was no increase in SRC numbers, indicating dissociation between the CD34+CD38− phenotype and SRC function. The underlying mechanism involved apparent downregulation of CD38 expression within a population of cultured CD34+CD38+ cells that no longer contained any SRC function. These results suggest that the relationship between stem cell function and cell surface phenotype may not be reliable for cultured cells. (Blood. 2000;95:102-110)

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