scholarly journals Tumor control by human cytomegalovirus in a murine model of hepatocellular carcinoma

2016 ◽  
Vol 3 ◽  
pp. 16012 ◽  
Author(s):  
Amit Kumar ◽  
Laurie Coquard ◽  
Sébastien Pasquereau ◽  
Laetitia Russo ◽  
Séverine Valmary-Degano ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Human Cytomegalovirus ◽  
Murine Model ◽  
Tumor Control

404: Immune Mediated Survival Advantage and Primary Tumor Control of Cryoablation Compared to Nephrectomy in a Murine Model of Advanced Renal Cancer

2006 ◽  
Vol 175 (4S) ◽  
pp. 132-132 ◽  
Author(s):  
Sean P. Hedican ◽  
Eric R. Wilkinson ◽  
Thomas F. Warner ◽  
Fred T. Lee ◽  
Stephen Y. Nakada
Keyword(s):  
Renal Cancer ◽  
Murine Model ◽  
Primary Tumor ◽  
Survival Advantage ◽  
Tumor Control ◽  
Advanced Renal Cancer ◽  
Immune Mediated

A murine model for non-alcoholic steatohepatitis showing evidence of association between diabetes and hepatocellular carcinoma

2013 ◽  
Vol 46 (3) ◽  
pp. 141-152 ◽  
Author(s):  
Masato Fujii ◽  
Yuichiro Shibazaki ◽  
Kyoko Wakamatsu ◽  
Yutaka Honda ◽  
Yusuke Kawauchi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Murine Model ◽  
Alcoholic Steatohepatitis

Allogeneic Vδ1 gamma delta T cells engineered with glypican-3 (GPC3)-specific CAR expressing soluble IL-15 have enhanced antitumor efficacy against hepatocellular carcinoma in preclinical models.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14511-e14511
Author(s):  
Amani Makkouk ◽  
Xue (Cher) Yang ◽  
Taylor Barca ◽  
Anthony Lucas ◽  
Mustafa Turkoz ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
T Cell ◽  
Healthy Donor ◽  
Cytokine Production ◽  
Tumor Control ◽  
Gamma Delta ◽  
T Cell Therapy ◽  
Donor Pbmcs

e14511 Background: Autologous αβ chimeric antigen receptor (CAR) T cell therapy has shown promising clinical results in hematologic malignancies but limited success in solid tumors. Allogeneic αβ T cell therapy may overcome several challenges faced by autologous therapy but carries the risk of graft-versus-host disease (GvHD) and does not readily recognize multiple tumor-associated antigens. Gamma delta (γδ) T cells are highly cytolytic effectors that can recognize and kill tumor cells in an MHC-unrestricted manner without causing GvHD. The Vδ1 subset is preferentially localized in peripheral tissue and is critical for tumor immunosurveillance. Engineering Vδ1 T cells with CARs can further enhance antitumor activity and represents an attractive and safe approach to treating solid tumors. However, their clinical use has been hindered by the limited number of circulating Vδ1 T cells. Here, we describe the development of the first allogeneic Vδ1 T cells that have been expanded from healthy donor PBMCs and genetically modified to secrete IL-15 (sIL15) and express a CAR targeting glypican-3 (GPC3), a rational target for hepatocellular carcinoma (HCC). Methods: Vδ1 T cells in healthy donor PBMCs were activated by a Vδ1-specific monoclonal antibody and transduced with 41BBζ or 41BBζ-sIL15 GPC3-CARs prior to cell expansion, αβ T cell depletion and cryopreservation. In vitro characterization included: 1) co-culture assays with GPC3-expressing HCC targets HepG2 and PLC/PRF/5, 2) phenotypic analysis by flow cytometry, and 3) cytokine production by multiplexed immunoassay. For in vivo assessment of tumor control, immunodeficient NSG mice were subcutaneously injected with HepG2 cells and treated with a single dose of 41BBζ or 41BBζ-sIL15 GPC3-CAR Vδ1 T cells. Additionally, tissues were harvested 7 days post transfer and analyzed by flow cytometry for Vδ1 T cell tissue homing and proliferation, or at end of study and analyzed for GvHD by immunohistochemistry. Results: Vδ1 T cells expanded over 10,000-fold and routinely reached >80% purity. Expanded Vδ1 T cells showed a primarily naïve-like phenotype (CD45RA+CD27+) with minimal exhaustion receptor expression and displayed robust proliferation, cytokine production, and cytotoxic activity against HCC cell lines expressing low and high GPC3 levels in vitro. In a HepG2 mouse model, GPC3-CAR Vδ1 T cells primarily accumulated and proliferated in the tumor, and a single dose was able to efficiently control tumor burden without causing GvHD. Importantly, 41BBζ-sIL15 GPC3-CAR Vδ1 cells displayed enhanced tumor-specific proliferation that resulted in better tumor control without any toxicity. Conclusions: Our results show that expanded Vδ1 T cells engineered with GPC3-CAR and sIL-15 represent a promising platform for safe and effective off-the-shelf treatment of HCC.

scholarly journals AAV6 Vexosomes Mediate Robust Suicide Gene Delivery in a Murine Model of Hepatocellular Carcinoma

2020 ◽  
Vol 17 ◽  
pp. 497-504 ◽  
Author(s):  
Nusrat Khan ◽  
Shubham Maurya ◽  
Sridhar Bammidi ◽  
Giridhara R. Jayandharan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Delivery ◽  
Murine Model ◽  
Suicide Gene

Su1958 A Novel Murine Model Recapitulates the Pathogenesis of Human Non-Alcoholic Steatohepatitis (NASH) and NASH-Related Hepatocellular Carcinoma

2012 ◽  
Vol 142 (5) ◽  
pp. S-546
Author(s):  
Masato Fujii ◽  
Yuichiro Shibazaki ◽  
Kyoko Wakamatsu ◽  
Taihei Honma ◽  
Taishi Hashiguchi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Murine Model ◽  
Alcoholic Steatohepatitis

Bone Marrow Mesenchymal Stem Cells Exhibit a Transdifferentiation and Therapeutic Effects in a Murine Model of Orthotopic Hepatocellular Carcinoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5133-5133
Author(s):  
Jun Ren ◽  
Hanfang Jiang ◽  
Lijun Di ◽  
Guohong Song
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Murine Model ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Tumor Diameter ◽  
Hepatic Differentiation ◽  
Marrow Mesenchymal Stem Cells

Abstract Background and Aim: Bone marrow stem cells can differentiate into mature hepatocytes in vitro and in vivo. Moreover, recent study shown bone marrow mesenchymal stem cells (MSCs) are the most potent component in hepatic differentiation, suggesting that the transplantation of MSCs is a promising treatment for liver disease. However, little information is available about the therapeutic potential of MSCs transplantation in cases of hepatic cell carcinoma (HCC). Here, we transplanted bone marrow-derived MSCs to testify their effects in a murine model of orthotopic HCC. Methods:MSCs were obtained from tow male strains of β-galactosidase (β-gal) transgenic mouse(Rosa 26) and BALB/c mouse. MSCs were injected into tumor in BALB/c femal murine models of orthotopic HCC. Tumor growths were assessed by MRI on 7 days and survival rates were observed. When mouse was dying, the liver was removed from each treated mouse and evaluated by x-gal staining, and immunohistochemisty as well. Results: MSCs transplantation increased the survival of hepatocellular carcinoma-bearing mice(25.5±4.5days verus 21.3±1.7days, p=0.025) and decreased tumor diameter slightly (7.7±2.9mm versus 9.4±2.8mm, p=0.284). MSCs transplanted directly into the tumor and/ or normal hepatic parenchyma in the same liver lobe localized mainly at the border between the tumor cells and normal liver parenchyma, induced a large area of coagulative necrosis in the tumor bed. Some engrafted MSCs were positive for albumin. There are in the carcinoma bearing BALB/c mice with MSCs implanted, whether MSCs from BALB/c mice or from Rosa 26 transgenic mice. Conclusion: Our results suggest that the therapeutical effects of MSCs might be mediated not only by their differentiation into hepatocyte, but also mainly by they possess intrinsic antineoplastic properties.

P.1.1: PREDICTIVE FACTORS FOR TUMOR CONTROL AMONG HEPATOCELLULAR CARCINOMA PATIENTS TREATED WITH SORAFENIB

2011 ◽  
Vol 43 ◽  
pp. S148 ◽  
Author(s):  
R. Tortora ◽  
A. Galeota Lanza ◽  
F. Lampasi ◽  
M. De Luca ◽  
M.T. Tartaglione ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Predictive Factors ◽  
Tumor Control
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