scholarly journals Herpesvirus saimiri strain 11 immortalizes a restricted marmoset T8 lymphocyte subpopulation in vitro.

1986 ◽  
Vol 164 (3) ◽  
pp. 926-931 ◽  
Author(s):  
M Kiyotaki ◽  
R C Desrosiers ◽  
N L Letvin
Keyword(s):  
Cell Lines ◽  
New World ◽  
Cell Function ◽  
Nk Cell ◽  
Common Marmoset ◽  
Primate Species ◽  
Herpesvirus Saimiri ◽  
New World Monkeys ◽  
Common Marmosets

Herpesvirus saimiri induces a fatal lymphoproliferative syndrome in a variety of New World primate species. We now show that cell lines derived from PBL of the common marmoset by in vitro-immortalization with H. saimiri strain 11 represent a remarkably restricted lymphocyte population. These cell lines have NK cell function, phenotypically express both suppressor/cytotoxic (T8) and NK cell (NKH1)-associated antigens, and express a T cell receptor. This subpopulation of lymphocytes is a very minor population of cells in the peripheral blood of common marmosets (less than or equal to 3%). The specificity in the interaction between H. saimiri strain 11 and a subpopulation of common marmoset lymphocytes represents an example of a restricted viral lymphotropism and may have important implications for the disease induced by this virus in New World monkeys.

scholarly journals STP and Tip Are Essential for Herpesvirus Saimiri Oncogenicity

1998 ◽  
Vol 72 (2) ◽  
pp. 1308-1313 ◽  
Author(s):  
S. Monroe Duboise ◽  
Jie Guo ◽  
Sue Czajak ◽  
Ronald C. Desrosiers ◽  
Jae U. Jung
Keyword(s):  
Cell Culture ◽  
Experimental Infection ◽  
Interleukin 2 ◽  
Common Marmoset ◽  
Herpesvirus Saimiri ◽  
Deletion Mutants ◽  
Wild Type ◽  
Common Marmosets ◽  
Mutant Forms

ABSTRACT Mutant forms of herpesvirus saimiri (HVS) subgroup C strain 488 with deletions in either STP-C488 or Tip were constructed. The transforming potentials of the HVS mutants were tested in cell culture and in common marmosets. Parental HVS subgroup C strain 488 immortalized common marmoset T lymphocytes in vitro to interleukin-2-independent growth, but neither of the deletion mutants produced such growth transformation. Wild-type HVS produced fatal lymphoma within 19 to 20 days of experimental infection of common marmosets, while HVS ΔSTP-C488 and HVS ΔTip were nononcogenic. Virus was repeatedly isolated from the peripheral blood of marmosets infected with mutant virus for more than 5 months. These results demonstrate that STP-C488 and Tip are not required for replication or persistence, but each is essential for transformation in cell culture and for lymphoma induction in common marmosets.

scholarly journals Identification of Postentry Restrictions to Mason-Pfizer Monkey Virus Infection in New World Monkey Cells

2008 ◽  
Vol 82 (22) ◽  
pp. 11140-11151 ◽  
Author(s):  
William E. Diehl ◽  
Elizabeth Stansell ◽  
Shari M. Kaiser ◽  
Michael Emerman ◽  
Eric Hunter
Keyword(s):  
Cell Lines ◽  
New World ◽  
Rhesus Macaques ◽  
World Monkey ◽  
Resistant Cell Line ◽  
Spider Monkey ◽  
Primate Species ◽  
New World Monkeys ◽  
Old World ◽  
New World Monkey

ABSTRACT TRIM5α has been shown to be a major postentry determinant of the host range for gammaretroviruses and lentiviruses and, more recently, spumaviruses. However, the restrictive potential of TRIM5α against other retroviruses has been largely unexplored. We sought to determine whether or not Mason-Pfizer monkey virus (M-PMV), a prototype betaretrovirus isolated from rhesus macaques, was sensitive to restriction by TRIM5α. Cell lines from both Old World and New World primate species were screened for their susceptibility to infection by vesicular stomatitis virus G protein pseudotyped M-PMV. All of the cell lines tested that were established from Old World primates were found to be susceptible to M-PMV infection. However, fibroblasts established from three New World monkey species specifically resisted infection by this virus. Exogenously expressing TRIM5α from either tamarin or squirrel monkeys in permissive cell lines resulted in a block to M-PMV infection. Restriction in the resistant cell line of spider monkey origin was determined to occur at a postentry stage. However, spider monkey TRIM5α expression in permissive cells failed to restrict M-PMV infection, and interference with endogenous TRIM5α in the spider monkey fibroblasts failed to relieve the block to infectivity. Our results demonstrate that TRIM5α specificity extends to betaretroviruses and suggest that New World monkeys have evolved additional mechanisms to restrict the infection of at least one primate betaretrovirus.

SGN-33, Lintuzumab, Demonstrates Anti-Leukemic Activity in Preclinical Models of AML.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 919-919
Author(s):  
May S.K. Sutherland ◽  
Changpu Yu ◽  
Carol Morris-Tilden ◽  
Timothy S. Lewis ◽  
Jamie B. Miyamoto ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Scid Mouse ◽  
Cell Function ◽  
Nk Cell ◽  
Fold Increase ◽  
In Vivo Studies ◽  
Specific Lysis

Abstract SGN-33 is a humanized IgG1 antibody with signaling properties that also mediates effector functions including Antibody-Dependent Cellular Cytotoxicity (ADCC). SGN-33 targets CD33, a sialoadhesion family member expressed on acute myeloid leukemia (AML) cells, eliciting complete remissions in some AML patients. In the laboratory, SGN-33 mediates natural killer (NK) cell lysis of both multi-drug resistant (MDR- positive) and MDR-negative AML cell lines. Additionally, SGN-33 significantly increases survival in SCID mouse disseminated models of MDR-negative and MDR- positive AML. Immunomodulatory compounds such as thalidomide and its analog, lenalidomide (Revlimid®), have been shown to enhance NK cell function and anti-cancer activity. In particular, Revlimid in combination with rituximab demonstrated greater tumor cell killing compared to the antibody alone. Given these reports, we investigated whether thalidomide or lenalidomide would enhance the anti-tumor effects of SGN-33. In vitro, lenalidomide augmented NK function in a dose-dependent fashion, manifested as significant increases in perforin expression. Thalidomide and lenalidomide enhanced ADCC activity (% maximal specific lysis) while having no significant effects on tumor cell levels of CD33. In vivo, treatment of SCID mice with lenalidomide resulted in a 2-fold increase in the absolute numbers of lymphocytes (including NK cells). In vivo studies evaluating the efficacy of the combination of SGN-33 and lenalidomide in SCID mouse models of AML are in progress. In summary, our studies demonstrate the anti-leukemic activity of SGN-33 against MDR-positive AML cell lines, suggesting that this unconjugated anti-CD33 antibody may yield benefit in clinical settings where other therapies fail due to the MDR phenotype of the tumor cells. Additionally, agents augmenting immunologic effector function might provide clinical benefit in combination with SGN-33. The combination of SGN-33 and lenalidomide is now being evaluated in a clinical trial.

scholarly journals GB virus B infection of the common marmoset (Callithrix jacchus) and associated liver pathology

2004 ◽  
Vol 85 (9) ◽  
pp. 2525-2533 ◽  
Author(s):  
James R. Jacob ◽  
Kuei-Chin Lin ◽  
Bud C. Tennant ◽  
Keith G. Mansfield
Keyword(s):  
Acute Hepatitis ◽  
New World ◽  
Antiviral Drug ◽  
Common Marmoset ◽  
Callithrix Jacchus ◽  
Primate Species ◽  
New World Primates ◽  
Common Marmosets ◽  
The Common ◽  
Human Primate

GB virus B (GBV-B) is a flavivirus that is related closely to hepatitis C virus (HCV) and induces an acute hepatitis when inoculated into several species of New World primates. Common marmosets (Callithrix jacchus) are a widely available, non-endangered primate species that is susceptible to GBV-B infection and develops a characteristic acute hepatitis. Here, animals were found to be susceptible to serially passaged serum and GBV-B transcripts. Hepatic pathology and peripheral viraemia could be quantified biochemically, immunophenotypically and morphologically, and persisted for periods of up to 6 months in some animals. Hepatitis was characterized by a marked influx of CD3+ CD8+ T lymphocytes and CD20+ B cells within the first 2 months of primary infection. The results of this study document the marmoset as another small, non-human primate species in which the pathogenesis of GBV-B can be studied and used as a surrogate model of HCV infection for investigation of pathogenesis and antiviral drug development.

scholarly journals Differential expression of GLUT2 in pancreatic islets and kidneys of New and Old World nonhuman primates

2009 ◽  
Vol 296 (3) ◽  
pp. R786-R793 ◽  
Author(s):  
Joshua Kramer ◽  
Elisabeth Ludlage Moeller ◽  
Audra Hachey ◽  
Keith G. Mansfield ◽  
Lynn M. Wachtman
Keyword(s):  
Pancreatic Islets ◽  
Nonhuman Primate ◽  
New World ◽  
Nonhuman Primates ◽  
Glucose Transporter ◽  
Health Concern ◽  
Primate Species ◽  
New World Monkeys ◽  
Common Marmosets ◽  
Old World

Diabetes is a growing public health concern, and animal models of this disease are necessary for a full understanding of disease pathogenesis, progression, clinical sequelae, and treatment options. In particular, nonhuman primate models of diabetes are important because of their close genetic relationship to humans. Although numerous Old World primate models have been described, few studies have examined the possibility of using New World monkeys as an animal model for this disease. Streptozotocin (STZ) is a common diabetogenic drug that selectively destroys beta cells after uptake via the GLUT2 glucose transporter. Induction of diabetes using STZ was attempted in common marmosets ( Callithrix jacchus). These animals showed increases in blood glucose consistent with diabetes only at STZ doses markedly greater than those used in other primate species. Additionally, all animals showed pathological evidence of acute renal and liver toxicity secondary to the treatment. In a subsequent comparative study of various nonhuman primates, GLUT2 immunostaining in pancreatic islets was used as a marker for sensitivity to STZ. Immunostaining of islets from a variety of nonhuman primate species indicated a reduced expression of pancreatic GLUT2 in New compared with Old World monkeys; this finding explains their resistance to diabetic induction with STZ. Furthermore, there were age-dependent differences in GLUT2 expression, with aged and infant macaques showing reduced expression. We conclude that New World monkeys are an inappropriate model for diabetes induction with STZ and that, with all primate species, it is important to consider the animals’ age before diabetic induction with STZ is attempted.

scholarly journals Sarcoma IL-12 overexpression facilitates NK cell immunomodulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mary Jo Rademacher ◽  
Anahi Cruz ◽  
Mary Faber ◽  
Robyn A. A. Oldham ◽  
Dandan Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Lines ◽  
Nk Cell ◽  
Autologous Tumor ◽  
Murine Models ◽  
Lentiviral Transduction ◽  
Ifn Γ ◽  
Human Sarcoma

AbstractInterleukin-12 (IL-12) is an inflammatory cytokine that has demonstrated efficacy for cancer immunotherapy, but systemic administration has detrimental toxicities. Lentiviral transduction eliciting IL-12-producing human sarcoma for autologous reintroduction provides localized delivery for both innate and adaptive immune response augmentation. Sarcoma cell lines and primary human sarcoma samples were transduced with recombinant lentivirus engineering expression of human IL-12 (hu-IL-12). IL-12 expressing sarcomas were assessed in vitro and in vivo following implantation into humanized NSG and transgenic human IL-15 expressing (NSG.Tg(Hu-IL-15)) murine models. Lentiviral transduction (LV/hu-IL-12) of human osteosarcoma, Ewing sarcoma and rhabdomyosarcoma cell lines, as well as low-passage primary human sarcomas, engendered high-level expression of hu-IL-12. Hu-IL-12 demonstrated functional viability, eliciting specific NK cell-mediated interferon-γ (IFN-γ) release and cytotoxic growth restriction of spheroids in vitro. In orthotopic xenograft murine models, the LV/hu-IL-12 transduced human sarcoma produced detectable IL-12 and elicited an IFN-γ inflammatory immune response specific to mature human NK reconstitution in the NSG.Tg(Hu-IL-15) model while restricting tumor growth. We conclude that LV/hu-IL-12 transduction of sarcoma elicits a specific immune reaction and the humanized NSG.Tg(Hu-IL-15) xenograft, with mature human NK cells, can define in vivo anti-tumor effects and systemic toxicities. IL-12 immunomodulation through autologous tumor transduction and reintroduction merits exploration for sarcoma treatment.

scholarly journals YB-1 Is Altered in Pregnancy-Associated Disorders and Affects Trophoblast in Vitro Properties via Alternation of Multiple Molecular Traits

2021 ◽  
Vol 22 (13) ◽  
pp. 7226
Author(s):  
Violeta Stojanovska ◽  
Aneri Shah ◽  
Katja Woidacki ◽  
Florence Fischer ◽  
Mario Bauer ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Progression ◽  
Cell Function ◽  
Trophoblast Cell ◽  
Mrna Levels ◽  
Trophoblast Cells ◽  
Invasion And Migration ◽  
And Migration ◽  
Apoptosis And Inflammation

Cold shock Y-box binding protein-1 (YB-1) coordinates several molecular processes between the nucleus and the cytoplasm and plays a crucial role in cell function. Moreover, it is involved in cancer progression, invasion, and metastasis. As trophoblast cells share similar characteristics with cancer cells, we hypothesized that YB-1 might also be necessary for trophoblast functionality. In samples of patients with intrauterine growth restriction, YB-1 mRNA levels were decreased, while they were increased in preeclampsia and unchanged in spontaneous abortions when compared to normal pregnant controls. Studies with overexpression and downregulation of YB-1 were performed to assess the key trophoblast processes in two trophoblast cell lines HTR8/SVneo and JEG3. Overexpression of YB-1 or exposure of trophoblast cells to recombinant YB-1 caused enhanced proliferation, while knockdown of YB-1 lead to proliferative disadvantage in JEG3 or HTR8/SVneo cells. The invasion and migration properties were affected at different degrees among the trophoblast cell lines. Trophoblast expression of genes mediating migration, invasion, apoptosis, and inflammation was altered upon YB-1 downregulation. Moreover, IL-6 secretion was excessively increased in HTR8/SVneo. Ultimately, YB-1 directly binds to NF-κB enhancer mark in HTR8/SVneo cells. Our data show that YB-1 protein is important for trophoblast cell functioning and, when downregulated, leads to trophoblast disadvantage that at least in part is mediated by NF-κB.

scholarly journals Cytokine-Induced Memory-Like NK Cells with High Reactivity against Acute Leukemia Blasts and Solid Tumor Cells Suitable for Adoptive Immunotherapy Approaches

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1577
Author(s):  
Matteo Tanzi ◽  
Michela Consonni ◽  
Michela Falco ◽  
Federica Ferulli ◽  
Enrica Montini ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Nk Cells ◽  
Tumor Cells ◽  
Cell Function ◽  
Nk Cell ◽  
Autologous Tumor ◽  
Lymphoid Leukemia ◽  
Hematopoietic Stem ◽  
Solid Malignancies

The limited efficacy of Natural Killer (NK) cell-based immunotherapy results in part from the suboptimal expansion and persistence of the infused cells. Recent reports suggest that the generation of NK cells with memory-like properties upon in vitro activation with defined cytokines might be an effective way of ensuring long-lasting NK cell function in vivo. Here, we demonstrate that activation with IL-12, IL-15 and IL-18 followed by a one-week culture with optimal doses of Interleukin (IL-2) and IL-15 generates substantial numbers of memory-like NK cells able to persist for at least three weeks when injected into NOD scid gamma (NSG) mice. This approach induces haploidentical donor-derived memory-like NK cells that are highly lytic against patients’ myeloid or lymphoid leukemia blasts, independent of the presence of alloreactive cell populations in the donor and with negligible reactivity against patients’ non-malignant cells. Memory-like NK cells able to lyse autologous tumor cells can also be generated from patients with solid malignancies. The anti-tumor activity of allogenic and autologous memory-like NK cells is significantly greater than that displayed by NK cells stimulated overnight with IL-2, supporting their potential therapeutic value both in patients affected by high-risk acute leukemia after haploidentical hematopoietic stem cell transplantation and in patients with advanced solid malignancies.

scholarly journals Rapid Generation of Single-Tumor Spheroids for High-Throughput Cell Function and Toxicity Analysis

2006 ◽  
Vol 11 (8) ◽  
pp. 922-932 ◽  
Author(s):  
Andrea Ivascu ◽  
Manfred Kubbies
Keyword(s):  
Tumor Cell ◽  
Suspension Culture ◽  
Cell Lines ◽  
Cell Function ◽  
Tumor Cell Lines ◽  
Proliferating Cells ◽  
Basement Membrane Extract ◽  
Rapid Generation ◽  
Size Heterogeneity

Spheroids are widely used in biology because they provide an in vitro 3-dimensional (3D) model to study proliferation, cell death, differentiation, and metabolism of cells in tumors and the response of tumors to radiotherapy and chemotherapy. The methods of generating spheroids are limited by size heterogeneity, long cultivation time, or mechanical accessibility for higher throughput fashion. The authors present a rapid method to generate single spheroids in suspension culture in individual wells. A defined number of cells ranging from 1000 to 20,000 were seeded into wells of poly-HEMA-coated, 96-well, round-or conical-bottom plates in standard medium and centrifuged for 10 min at 1000 g. This procedure generates single spheroids in each well within a 24-h culture time with homogeneous sizes, morphologies, and stratification of proliferating cells in the rim and dying cells in the core region. Because a large number of tumor cell lines form only loose aggregates when cultured in 3D, the authors also performed a screen for medium additives to achieve a switch from aggregate to spheroid morphology. Small quantities of the basement membrane extract Matrigel, added to the culture medium prior to centrifugation, most effectively induced compact spheroid formation. The compact spheroid morphology is evident as early as 24 h after centrifugation in a true suspension culture. Twenty tumor cell lines of different lineages have been used to successfully generate compact, single spheroids with homogenous size in 96-well plates and are easily accessible for subsequent functional analysis.

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