Th17 lymphocyte‐dependent degradation of joint cartilage by synovial fibroblasts in a humanized mouse model of arthritis and reversal by secukinumab

2020 ◽  
Author(s):  
Francesca Margheri ◽  
Laura Maggi ◽  
Alessio Biagioni ◽  
Anastasia Chillà ◽  
Anna Laurenzana ◽  
...  
Keyword(s):  
Mouse Model ◽  
Synovial Fibroblasts ◽  
Joint Cartilage ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Th17 Lymphocyte

scholarly journals Preclinical platform for long-term evaluation of immuno-oncology drugs using hCD34+ humanized mouse model

2020 ◽  
Vol 8 (2) ◽  
pp. e001513
Author(s):  
Nahee Park ◽  
Kamal Pandey ◽  
Sei Kyung Chang ◽  
Ah-Young Kwon ◽  
Young Bin Cho ◽  
...  
Keyword(s):  
Mouse Model ◽  
Humanized Mice ◽  
Preclinical Models ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Durable Response ◽  
Term Efficacy ◽  
Nsg Mice ◽  
Oncology Research

BackgroundWell-characterized preclinical models are essential for immune-oncology research. We investigated the feasibility of our humanized mouse model for evaluating the long-term efficacy of immunotherapy and biomarkers.MethodsHumanized mice were generated by injecting human fetal cord blood-derived CD34+ hematopoietic stem cells to NOD-scid IL2rγnull (NSG) mice myeloablated with irradiation or busulfan. The humanization success was defined as a 25% or higher ratio of human CD45+ cells to mice peripheral blood mononuclear cells.ResultsBusulfan was ultimately selected as the appropriate myeloablative method because it provided a higher success rate of humanization (approximately 80%) and longer survival time (45 weeks). We proved the development of functional T cells by demonstrating the anticancer effect of the programmed cell death-1 (PD-1) inhibitor in our humanized mice but not in non-humanized NSG mice. After confirming the long-lasting humanization state (45 weeks), we further investigated the response durability of the PD-1 inhibitor and biomarkers in our humanized mice. Early increase in serum tumor necrosis factor α levels, late increase in serum interleukin 6 levels and increase in tumor-infiltrating CD8+ T lymphocytes correlated more with a durable response over 60 days than with a non-durable response.ConclusionsOur CD34+ humanized mouse model is the first in vivo platform for testing the long-term efficacy of anticancer immunotherapies and biomarkers, given that none of the preclinical models has ever been evaluated for such a long duration.

scholarly journals LFA-1-targeting Leukotoxin (LtxA; Leukothera®) causes lymphoma tumor regression in a humanized mouse model and requires caspase-8 and Fas to kill malignant lymphocytes

2015 ◽  
Vol 39 (6) ◽  
pp. 649-656 ◽  
Author(s):  
Kristina M. DiFranco ◽  
Nadine Johnson-Farley ◽  
Joseph R. Bertino ◽  
David Elson ◽  
Brian A. Vega ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tumor Regression ◽  
Caspase 8 ◽  
Humanized Mouse ◽  
Humanized Mouse Model
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