A functional DC cross talk promotes human ILC homeostasis in humanized mice

Key Points GARP efficiently represses proliferation of naïve and resting CD4+ T cells and is involved in the induction of adaptive regulatory T cells. In vivo, GARP prevents T cell–mediated destructive inflammation in a preclinical humanized mouse model of GVHD.

Download Full-text

A novel humanized mouse model with significant improvement of class-switched, antigen-specific antibody production

Blood ◽

10.1182/blood-2016-04-709584 ◽

2017 ◽

Vol 129 (8) ◽

pp. 959-969 ◽

Cited By ~ 40

Author(s):

Hua Yu ◽

Chiara Borsotti ◽

Jean-Nicolas Schickel ◽

Shu Zhu ◽

Till Strowig ◽

...

Keyword(s):

Mouse Model ◽

High Specificity ◽

Memory B Cells ◽

Humanized Mice ◽

Antibody Repertoire ◽

Humanized Mouse ◽

Humanized Mouse Model ◽

Cell Engraftment ◽

Key Points ◽

Specific Antibody Production

Key Points Human IL-6 improves T-cell engraftment and serum IgG production in humanized mice. IgG-switched memory B cells in IL-6 knock-in mice displayed a diverse antibody repertoire and high specificity against immunized antigen.

Download Full-text

Activation of the erythroid K-Cl cotransporter Kcc1 enhances sickle cell disease pathology in a humanized mouse model

Blood ◽

10.1182/blood-2014-10-609362 ◽

2015 ◽

Vol 126 (26) ◽

pp. 2863-2870 ◽

Cited By ~ 11

Author(s):

Fiona C. Brown ◽

Ashlee J. Conway ◽

Loretta Cerruti ◽

Janelle E. Collinge ◽

Catriona McLean ◽

...

Keyword(s):

Sickle Cell Disease ◽

Mouse Model ◽

Missense Mutation ◽

Sickle Cell ◽

Cytoplasmic Tail ◽

Cell Disease ◽

Humanized Mouse ◽

Humanized Mouse Model ◽

Key Points

Key Points A missense mutation in the cytoplasmic tail of Kcc1 activates K-Cl cotransporter activity by impairing phosphorylation of nearby threonines. In vivo evidence shows that activation of Kcc1 directly contributes to the pathogenesis of sickle cell disease.

Download Full-text

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

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001513 ◽

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.

Download Full-text

Evidence from a humanized mouse model of androgenetic alopecia that platelet‐rich plasma (PRP) stimulates hair regrowth, hair shaft diameter and vellus‐to‐terminal hair reconversion in vivo

British Journal of Dermatology ◽

10.1111/bjd.20084 ◽

2021 ◽

Author(s):

R. Laufer Britva ◽

A. Keren ◽

A. Ginzburg ◽

Y. Ullmann ◽

R. Paus ◽

...

Keyword(s):

Mouse Model ◽

Platelet Rich Plasma ◽

Hair Shaft ◽

Androgenetic Alopecia ◽

Humanized Mouse ◽

Humanized Mouse Model ◽

Terminal Hair ◽

Hair Regrowth ◽

Shaft Diameter

Download Full-text

P06.07 In vivo studies of immunomodulatory a-CTLA-4 antibody in a humanized mouse model

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-itoc8.41 ◽

2021 ◽

Vol 9 (Suppl 1) ◽

pp. A22.1-A22

Author(s):

C Reitinger ◽

F Nimmerjahn

Keyword(s):

Immune System ◽

Mouse Model ◽

Cancer Immunotherapy ◽

Model Systems ◽

Checkpoint Control ◽

Human Immune System ◽

Humanized Mouse ◽

Humanized Mouse Model ◽

Human Immune

BackgroundRecent findings in cancer immunotherapy have reinforced the hypothesis that the immune system is able to control most cancers. Immunomodulatory antibodies can enhance immune responses, having the potential to generate anti-cancer immunity.1–4Materials and MethodsMost current studies addressing this question are performed in murine mouse model systems or use in vitro culture systems, which do not reflect the human in vivo situation, potentially leading to results that cannot be fully translated into human cancer therapy. Therefore, it is necessary to establish a new mouse model, which allows the study of cancer immunotherapy in the context of a human immune system. We focused on the establishment of a humanized mouse model, in which different immunomodulatory antibodies can be tested in the presence of a human immune system.ResultsFirst experiments concerning the suitability to test immunomodulatory antibodies in the humanized mouse model, revealed that effects of checkpoint-control antibody a-CTLA-4 were similar to the effects seen in patients of clinical studies. To analyse the anti-tumor activities of immunomodulatory antibodies in vivo we are establishing a human melanoma-like tumor model in humanized mice.ConclusionsThis enables us to test the efficacy of immunomodulatory agonistic antibodies (such as CP-870,893) and checkpoint control antibodies (such as anti-CTLA-4) in eliminating a melanoma-like tumor. Furthermore, parameters like tumor infiltrating human cells und cytokine/chemokine production can be analysed.ReferencesSchuster M, Nechansky A, Loibner H. Cancer immunotherapy. Biotechnol J 2006;1:138–147.Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature rev 2011;480:480–489.Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Annals of Oncology 2012;23:vii6–vii9.Langer LF, Clay TM, Morse MA. Update on anti-CTLA-4 in clinical trials. Expert Opin Biol Ther 2007;8:1245–1256.Disclosure InformationC. Reitinger: None. F. Nimmerjahn: None.

Download Full-text