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hPD-1/hTIM3
Humanized mice (target-specific)

Preclinical double-humanized PD-1/TIM3 mouse model

The hPD-1/hTIM3 mouse enables the in vivo efficacy assessment and profiling of immuno-oncology agents targeting the human immune checkpoint PD-1 and/or TIM3 in fully immunocompetent mice.

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Design of the hPD‑1/hTIM3 mouse

The double-humanized PD-1 and TIM3 mouse model (hPD-1/hTIM3) was generated by intercrossing hPD-1 and hTIM3 mice.

hPD-1 has been developed by inserting, within the mouse PD-1 locus, a chimeric PD-1 with a human extracellular domain, a murine transmembrane domain and a murine intracellular domain.

The design of the TIM3 humanized model, developed by Knockin at the mouse TIM3 locus, enables the expression of a chimeric TIM3 with a human extracellular domain, a murine transmembrane domain and a murine intracellular domain.

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hPD-1/hTIM3 features

  • The PD-1 and TIM3 extracellular domains are entirely humanized
  • Preservation of the target-ligand interaction
  • Fully functional mouse immune system
  • Lack of expression of the murine target gene, thus avoiding cross-reactivity

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(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

Multispecific CD73/PD-1 targeting

Apr 2024
(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

Apr 2024
(Anaveon) ANV600 is a novel PD-1 targeted IL-2Rβ/γ agonist that is combinable with therapeutic PD-1 inhibitors

Novel PD-1 targeted IL-2Rβ/γ agonist

Nov 2023
(Anaveon) ANV600 is a potent, cis-signaling, IL-2Rβ/γ directed IL-2 which efficiently expands intratumoral stem-like CD8 T cells

PD-1 & strong tumor growth inhibition

Apr 2023
(Reaction Biology) Humanized PD-1 knock-in mice as a model system for combination therapies with human specific PD-1 therapeutics

hPD-1 to evaluate novel cancer therapies

Apr 2023
(Charles River) Novel in vivo preclinical humanized models for the evaluation of human specific immune checkpoint inhibitors.

hPD-1/hCTLA-4 mice to evaluate immune checkpoint inhibitors

Nov 2019
(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

Mar 2019
Human PD-1 agonist treatment alleviates neutrophilic asthma by reprogramming T cells

J Allergy Clin Immunol

Jan 2023
An anti-PD-1–GITR-L bispecific agonist induces GITR clustering-mediated T cell activation for cancer immunotherapy

Nat Cancer

Jan 2022
Highlighted article
read the comment
Therapeutic targeting of PD-1/PD-L1 blockade by novel small-molecule inhibitors recruits cytotoxic T cells into solid tumor microenvironment

J Immunother Cancer

Jan 2022
Design and Efficacy of a Monovalent Bispecific PD-1/CTLA4 Antibody That Enhances CTLA4 Blockade on PD-1 + Activated T Cells

Cancer Discov

Jan 2021
VISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response

VISTA - safety and PK profiling

8 min read
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Apr 2024
CCX559 is a potent, orally-administered small molecule PD-L1 inhibitor that induces anti-tumor immunity

Humanized ICP mouse and cell lines

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Jun 2023
A new promising family of small molecules regulating the PD-L1/PD-1 signaling pathway

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

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Jul 2022
An alternative approach to immunotherapy: A bispecific agonist

Humanized PD-1 & GITR mouse

4 min read
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Mar 2022
Uncoupling efficacy from toxicity: a case study on MEDI5752

Bispecific antibodies

5 min read
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Apr 2021
No results

Validation data

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Preclinical double-humanized PD-1/TIM3 mouse model

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