Humanized mice (target-specific)

Well-established mouse lines that allow in vivo efficacy and safety assessment of biologics and other compounds.

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Applications

These models are suitable to assess the efficacy of compounds targeting human proteins in fully immunocompetent mice. Moreover, they represent a powerful model system for studying how compounds modulate cell response and/or stroma cells in a physiological microenvironment.

General model features

Physiological expression of the human target(s)
Preservation of the target-ligand interaction
Fully functional mouse immune system
Lack of expression of the murine target gene, thus avoiding cross-reactivity

Related resources and publications

osteomyelitis

hyperalgesia

PET imaging

intrauterine growth deficiency

Myopia

ossification

cGAS

cGAS-STING pathway

TFRC

FX-deficiency

muscle-eye-brain disease (MEB)

Tumor microenvironment

primary immunodeficiency (PID)

Oncology

Pharmacology

Neuroscience

Metabolism

Inflammation

Immunology

Respiration

Cardiovascular

Ophthalmology

Nephrology

Musculoskeletal

Hematology

Epigenetics

Development

Endocrinology

Dermatology

Humanization

Rosa26

TET system

Hprt

CreERt2

FLEx

innate immunity

Transgenesis

infection

vision

immune response

dementia

central nervous system (CNS)

taste

transplantation

autoimmunity

thermoregulation

sugar homeostasis

stress

skelet

pulmonary research

nutrition

pain research

muscle research

locomotion

memory

hearing

fat homeostatsis

tissue research

epigentic modification

drugs

cancer research

cell research

behavior

aging

stem cell research

reproductive research

lymphatic system

learning

heart research

gut research

genetic research

exercise

bone research

embryonic development

dental research

blood research

von Willebrand disease (VWD)

X-linked adrenoleukodystrophy (X-ADL)

Vanishing White Matter (VWM) disease

type 2 diabetes (T2D)

ulcerative colitis (UC)

type 1 diabetes (T1D)

thrombosis

thrombocytopenia

systemic lupus erythematosus (SLE)

tauopathy

stenosis

steatohepatitis

spinocerebellar ataxia type 2 (SCA2)

small cell lung cancer

SHORT syndrome

sepsis

schizophrenia

Senescence-associated secretory phenotype (SASP)

seizure

sarcoidosis

rhesus-deficiency syndrome

retinopathy

retinitis pigmentosa (RP)

retinal dystrophy disorder

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(Sensei) Conditionally active CD28xVISTA bispecific antibodies induce myeloid-driven tumor-specific T-cell co-stimulation for improved cancer immunotherapy

CD28xVISTA bispecific antibodies in immunotherapy

(Bonum) A Novel Method for Generating Regulated Cytokine Therapeutics: Safety and Activity of a Conditionally Active cLAG3-IL2 Capable of Delivering IL-2 to LAG-3+ Cells While Remaining Inert on LAG-3- Cells

Safety and activity of a conditionally active cLAG3-IL2

(Cidara) Discovery of a multispecific CD73/PD-1 targeting Drug Fc-Conjugate (DFC), which improves tumor reduction compared to PD-1 monotherapy in a humanized mouse model

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Novel FcγR humanized mouse models enabling efficacy and PK/PD of therapeutic antibodies

FcγR mouse models for efficacy and PK/PD

CD28 humanized mouse model for efficacy and safety assessment of CD28-targeting therapies

CD28-targeting therapies

Novel TFRC humanized mouse model for drug delivery to the brain

Drug delivery to the brain (TFRC)

Cell-depleting agents assessment in preclinical models

BRGSF-HIS & hFcγR to assess cell depletion

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(Anaveon) ANV600 is a novel PD-1 targeted IL-2Rβ/γ agonist that is combinable with therapeutic PD-1 inhibitors

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(VIB) A Cross-Species Map and Humanized Mouse Model of Fcγ Receptors and FcRn

Humanized Mouse Model of Fcγ Receptors

(Reaction Biology) Humanized PD-1 knock-in mice as a model system for combination therapies with human specific PD-1 therapeutics

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(Anaveon) ANV600 is a potent, cis-signaling, IL-2Rβ/γ directed IL-2 which efficiently expands intratumoral stem-like CD8 T cells

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(Maxivax) Sustained delivery of low-dose anti-CTLA-4 by genetically engineered encapsulated cells drives tumor response and prolongs survival in a colorectal cancer model

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(Arcus) AB598, a Therapeutic Anti-Human CD39 Antibody, Binds and Inhibits CD39 Enzymatic Activity In Vivo to Promote Anti-Tumor Immunity

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CD3 humanized mouse models as validated tools to assess immune-related adverse events of T-cell engagers

CD3 and BRGSF-HIS to assess IrAEs

Anti-VISTA agents profiling: complementarity of BRGSF-HIS and hVISTA Knock-in as preclinical models for immunotherapies

BRGSF-HIS & hVISTA for immunotherapies

(Sensei) SNS-101, a monoclonal antibody that is highly selective for VISTA in the tumor microenvironment, demonstrates favorable pharmacokinetic and cytokine release characteristics and potentiates anti-PD-1 responsiveness

VISTA in the tumor microenvironment

(Curadev) Intravenous administration of the small molecule STING agonist CRD5500 elicits potent anti-tumor immune responses in cold tumors

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Translatable preclinical mouse models for assessment of T-cell engager-induced CRS

BRGSF-HIS & CD3ε in CRS

(Kineta) A Fully Human anti-VISTA Antibody as a Promising Therapy Against Poorly Immunogenic Tumors

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(Charles River) Enhanced anti-tumor lymphocyte function and frequencies measured by multichromatic flow cytometry in human CTLA-4 knock-in mice in a colorectal carcinoma model after treatment with ipilimumab

hCTLA-4 mice as a colorectal carcinoma model

(Charles River) Validation of humanized PD-1 knock-in mice as an emerging model to evaluate human specific PD-1 therapeutics

hPD-1 mice as a model to evaluate human specific PD-1 therapeutics

NI-3201 Is a Bispecific Antibody Mediating PD-L1-Dependent CD28 Co-stimulation on T Cells for Enhanced Tumor Control

Cancer Immunol Res

In-depth cross-validation of human and mouse CD4-specific minibodies for noninvasive PET imaging of CD4+ cells and response prediction to cancer immunotherapy

Theranostics

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Targeting of immune checkpoint regulator V-domain Ig suppressor of T-cell activation (VISTA) with 89Zr-labelled CI-8993

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Agonistic anti-DCIR antibody inhibits ITAM-mediated inflammatory signaling and promotes immune resolution

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Differential effects of FcRn antagonists on the subcellular trafficking of FcRn and albumin

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HPN328, a Trispecific T Cell-activating Protein Construct Targeting DLL3-Expressing Solid Tumors

Mol Cancer Ther

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VISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response

Nat Commun

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Common single-base insertions in the VNTR of the carboxyl ester lipase (CEL) gene are benign and also likely to arise somatically in the exocrine pancreas

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Myeloid and dendritic cells enhance therapeutics-induced cytokine release syndrome features in humanized BRGSF-HIS preclinical model

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Rational design of a genomically humanized mouse model for dominantly inherited hearing loss, DFNA9

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Two birds with one stone: human SIRPα nanobodies for functional modulation and in vivo imaging of myeloid cells

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Mistranslation-associated perturbations of proteostasis do not promote accumulation of amyloid beta and plaque deposition in aged mouse brain

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Front Immunol

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Widespread monoclonal IgE antibody convergence to an immunodominant, pro-anaphylactic Ara h 2 epitope in peanut allergy

J Allergy Clin Immunol

Transgenic expression of the HERV-W envelope protein leads to polarized glial cell populations and a neurodegenerative environment

Proc Natl Acad Sci U S A

SRF617 Is a Potent Inhibitor of CD39 with Immunomodulatory and Antitumor Properties

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CCX559 is a potent orally-administered small molecule PD-L1 inhibitor that induces anti-tumor immunity

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A gain-of-function filamin A mutation in mouse platelets induces thrombus instability

J Thromb Haemost

The genetic risk factor CEL-HYB1 causes proteotoxicity and chronic pancreatitis in mice

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An albumin-angiotensin converting enzyme 2-based SARS-CoV-2 decoy with FcRn-driven half-life extension

Acta Biomater

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Hyaluronan Synthase 3 is Protective After Cardiac Ischemia-Reperfusion by preserving the T cell Response

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Single-Domain Antibodies for Targeting, Detection, and In Vivo Imaging of Human CD4+ Cells

Front Immunol

IgG against the membrane-proximal portion of the desmoglein 3 ectodomain induces loss of keratinocyte adhesion, a hallmark in pemphigus vulgaris

J Invest Dermatol

Human PD-1 agonist treatment alleviates neutrophilic asthma by reprogramming T cells

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Enhanced half-life and antitumor activity of Interleukin-15 through genetic fusion of a serum albumin-specific protein binder

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Therapeutic targeting of PD-1/PD-L1 blockade by novel small-molecule inhibitors recruits cytotoxic T cells into solid tumor microenvironment

J Immunother Cancer

Brain-derived neurotrophic factor expression in serotonergic neurons improves stress resilience and promotes adult hippocampal neurogenesis

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Modification of BRCA1-associated breast cancer risk by HMMR overexpression

Nat Commun

An anti-PD-1–GITR-L bispecific agonist induces GITR clustering-mediated T cell activation for cancer immunotherapy

Nat Cancer

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A hotspot mutation targeting the R-RAS2 GTPase acts as a potent oncogenic driver in a wide spectrum of tumors

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Humanization of a strategic CD3 epitope enables evaluation of clinical T-cell engagers in a fully immunocompetent in vivo model

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Overexpression of wild type RRAS2, without oncogenic mutations, drives chronic lymphocytic leukemia

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Caspase-6-cleaved Tau fails to induce Tau hyperphosphorylation and aggregation, neurodegeneration, glial inflammation, and cognitive deficits

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Danuglipron (PF-06882961) in type 2 diabetes: a randomized, placebo-controlled, multiple ascending-dose phase 1 trial

Nat Med

Loss of sphingosine kinase 2 enhances Wilm's tumor suppressor gene 1 and nephrin expression in podocytes and protects from streptozotocin-induced podocytopathy and albuminuria in mice.

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Albumin protects the liver from tumor necrosis factor α-induced immunopathology

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In Vivo Half-Life Extension of BMP1/TLL Metalloproteinase Inhibitors Using Small-Molecule Human Serum Albumin Binders

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Gain-of-function factor H–related 5 protein impairs glomerular complement regulation resulting in kidney damage

Proc Natl Acad Sci U S A

Design and Efficacy of a Monovalent Bispecific PD-1/CTLA4 Antibody That Enhances CTLA4 Blockade on PD-1 + Activated T Cells

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Visualization of Mineral-Targeted Alkaline Phosphatase Binding to Sites of Calcification In Vivo

J Bone Miner Res

Biased M1-muscarinic-receptor-mutant mice inform the design of next-generation drugs

Nat Chem Biol

VISTA is an acidic pH-selective ligand for PSGL-1

Nature

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VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance

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Chemogenetics defines receptor-mediated functions of short chain free fatty acids

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The CTLA-4 x OX40 bispecific antibody ATOR-1015 induces anti-tumor effects through tumor-directed immune activation

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Molybdenum cofactor deficiency type B knock-in mouse models carrying patient-identical mutations and their rescue by singular AAV injections

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Histological and behavioural phenotypes of a novel mutated APP knock-in mouse

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An ancestral retroviral protein identified as a therapeutic target in type-1 diabetes

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Overexpression of tissue-nonspecific alkaline phosphatase (TNAP) in endothelial cells accelerates coronary artery disease in a mouse model of familial hypercholesterolemia.

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Hyaluronan synthase 3 promotes plaque inflammation and atheroprogression

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Paired Siglec receptors generate opposite inflammatory responses to a human‐specific pathogen.

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Selective Enhancement of Insulin Sensitivity in the Endothelium In Vivo Reveals a Novel Proatherosclerotic Signalling Loop.

Circ Res

Tauopathy induced by low level expression of a human brain-derived tau fragment in mice is rescued by phenylbutyrate

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C26:0-Carnitine Is a New Biomarker for X-Linked Adrenoleukodystrophy in Mice and Man.

PLoS One

An antibody biosensor establishes the activation of the M1 muscarinic acetylcholine receptor during learning and memory

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Transgenic Overexpression of Tissue-Nonspecific Alkaline Phosphatase (TNAP) in Vascular Endothelium Results in Generalized Arterial Calcification.

J Am Heart Assoc

Generation of a double transgenic humanised neonatal Fc receptor (FcRn)/albumin mouse to study the pharmacokinetics of albumin-linked drugs

J Control Release

Deletion of Hyaluronan Synthase 3 Inhibits Neointimal Hyperplasia in Mice.

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In vivo structure‐function studies of human hepatic lipase: the catalytic function rescues the lean phenotype of HL‐deficient (hl−/−) mice

Physiol Rep

Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo

Blood

Pathophysiological role of vascular smooth muscle alkaline phosphatase in medial artery calcification

J Bone Miner Res

Knock-In of Human BACE1 Cleaves Murine APP and Reiterates Alzheimer-like Phenotypes

J Neurosci

Caspase-6 activity in the CA1 region of the hippocampus induces age-dependent memory impairment

Cell Death Differ

Spatial learning impairments in PLB1Triple knock-in Alzheimer mice are task-specific and age-dependent.

Cell Mol Life Sci

The human NPM1 mutation A perturbs megakaryopoiesis in a conditional mouse model

Blood

Novel role of the IGF-1 receptor in endothelial function and repair: studies in endothelium-targeted IGF-1 receptor transgenic mice.

Diabetes

Abnormal Cognition Sleep EEG and Brain Metabolism in a Novel Knock-In Alzheimer Mouse PLB1.

PLoS One

Drug targeting to monocytes and macrophages using esterase-sensitive chemical motifs.

J Pharmacol Exp Ther

A new Nature report by Bristol-Myers Squibb provides new insights into VISTA biology and design of combination therapies

Humanized ICP in immuno-oncology

Part 1: Toward a better effective preclinical model in immuno-oncology

Immuno-oncolology models

A VISTA on naive T cell fate

Humanized ICP mouse

Part 4: Humanized immune checkpoint mouse models for immuno-oncology studies

Immuno-oncolology models

HSA/hFcRn, a powerful model for your PK/PD studies

Immuno-oncolology models

Define “humanized”: two mouse models helping produce cancer immunotherapies

Humanized mouse models

A novel preclinical and translational humanized CD3ε model to study the efficacy of T-cell engagers

T-cell engager

Uncoupling toxicity from therapeutic efficacy: the new challenge of immunotherapies

Assess toxicity with ICP

Relevant preclinical models to test T-cell engagers: The case of CD28

T-cell engager

An alternative approach to immunotherapy: A bispecific agonist

Humanized PD-1 & GITR mouse

Humanization of a strategic CD3 epitope enables evaluation of clinical T-cell engagers in a fully immunocompetent in vivo model

T-cell engager CD3

Assessing T-cell engagers in vivo: How BRGSF-HIS mice can help

Assess T-cell engager in BRGSF-HIS

A new promising family of small molecules regulating the PD-L1/PD-1 signaling pathway

Humanized PD-1/PD-L1 mouse and cell line

An albumin-angiotensin converting enzyme 2-based SARS-CoV-2 decoy with FcRn-driven half-life extension

Humanized HSA/hFcRn mouse

CCX559 is a potent, orally-administered small molecule PD-L1 inhibitor that induces anti-tumor immunity

Humanized ICP mouse and cell lines

Assessing T-cell engagers efficacy in vivo: Versatility of BRGSF-HIS mice

Assess T-cell engager in BRGSF-HIS

A highly potent anti-VISTA antibody KVA12123 - a new immune checkpoint inhibitor and a promising therapy against poorly immunogenic tumors

Humanized VISTA mouse & Pharmacokinetics

An engineered humanized common light chain mouse model to develop bispecific antibodies

Humanized cLC model - Bispecific antibody development

Development of a new hSIRPα-specific radiotracer for non-invasive PET imaging using genOway’s double humanized hCD47/hSIRPα mouse and MC38-hPD-L1-hCD47-LZ cell line

Targeting the human CD47/SIRPα axis

BRGSF-HIS: genOway’s mouse model to evaluate the pathogenesis of Staphylococcus aureus Panton-Valentine leukocidin in acute implant-associated osteomyelitis

BRGSF-HIS as model for acute implant-associated osteomyelitis

VISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response

VISTA - safety and PK profiling

HPN328, a new T cell–activating construct for treating solid tumors

CD3ε - T-cell engager assessment

Development of a new antibody-drug conjugate against CD71, INA03, for the treatment of leukemia

TFRC for anti-cancer therapies

New CD4-specific minibodies to predict cancer treatment outcomes

CD4 for cancer treatment outcomes

A radiolabeled VISTA antibody for imaging VISTA expression

hVISTA - antibodies & PET imaging

Immunocompromised human serum albumin/human neonatal Fc receptor mouse model: A new xenograft model for efficacy studies of immunotherapies

Therapeutic efficacy and pharmacokinetics

The importance of genetic design when choosing your preclinical model - A Case Study on GLP-1R

Physiological relevancy in preclinical models

Uncoupling efficacy from toxicity: a case study on MEDI5752

Bispecific antibodies

Uncoupling toxicity from therapeutic efficacy: a case study on ATOR-1015

Bispecific antibodies

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Other categories

Immunodeficient rodents

Explore our immunodeficient models, featuring cutting-edge strains like BRGSF mouse and SDRG rat.

Humanized mice (HIS/human immune system)

Address human-specific questions in a more relevant manner, facilitating translational research in several biomedical disciplines and approaches.

Cell lines

Our humanized & Knockout ICP cell lines can be used for in vivo tumor growth assays in syngeneic models and in vitro mechanistic studies.

Knockout and reporter models

Our off-the-shelf Knockout & reporter models are well established, validated and widely used mouse and rat lines.