Programmed cell death 1 ligand 1 (PD-L1), also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7H1), is an immune inhibitory receptor ligand. PD-L1 is a type I transmembrane protein with immunoglobulin V-like (IgV) and C-like (IgC) structural domains and is expressed by hematopoietic and non-hematopoietic cells, including T cells, B cells, and various types of tumor cells ^[1]. PD-L1 can bind to PD-1 on the surface of CD8+ T cells, inhibiting the activity of CD8+ T cells. This interaction can prevent the immune system from damaging normal tissues, but it can also be used by tumor cells to escape immune surveillance. Monoclonal antibodies that competitively bind to PD-L1 can relieve the immune function inhibition mediated by the binding of PD-1 and PD-L1. This can reactivate CD8+ T cells, triggering the human body's anti-tumor immune response ^[2]. Therefore, the development of antibody drugs targeting PD-1 and PD-L1 is a hot area in tumor immunotherapy. This strain is a humanized model of the mouse Pdl1 gene in which the gene sequence encoding the extracellular domain (immunoglobulin V-like, IgV-like) of mouse PD-L1 protein is replaced with the corresponding human PD-L1 gene sequence. B6-hPDL1-V(2) mice can be used for the research of PD-L1 targeted drug development screening, efficacy and safety evaluation, tumor immunotherapy evaluation, and immune system mechanisms ^[2-4]. It is important to note that B6-hPDL1-V(2) mice were engineered utilizing an identical genetic modification strategy as the B6-hPDL1-V strain (Catalog Number: C001420), with their sole distinction lying in their genetic background.

The TNFRSF9 gene, also known as 4-1BB/CD137, encodes a protein that belongs to the TNF receptor superfamily. This receptor aids in the clonal expansion, survival, and development of T cells. It can also induce the proliferation of peripheral monocytes, enhance TCR/CD3-triggered activation-induced T cell apoptosis, and regulate CD28 co-stimulation to promote Th1 cell responses. TRAF adaptor proteins can bind to it and transmit signals that activate NF-kappaB. Many immune cell types express TNFRSF9, including activated NK cells, NKT cells, B cells, eosinophils, basophils, mast cells, neutrophils, mature Tregs, activated monocytes, and dendritic cells. Additionally, TNFRSF9 may be expressed in non-immune cell types such as endothelial cells, neurons, astrocytes, and microglia. TNFRSF9 plays roles in innate and adaptive immunity, including cancer immunology and autoimmune diseases ^[1]. Due to its broad expression profile and immune response functions, 4-1BB is a potential target for cancer and immunotherapy. In recent years, research on second-generation 4-1BB agonists has been expanding, with various strategies being implemented to overcome the liver toxicity and efficacy limitations of the first generation ^[2-3]. Programmed cell death 1 ligand 1 (PD-L1), also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7H1), is an immune inhibitory receptor ligand. PD-L1 is a type I transmembrane protein with immunoglobulin V-like (IgV) and C-like (IgC) structural domains and is expressed by hematopoietic and non-hematopoietic cells, including T cells, B cells, and various types of tumor cells ^[4]. PD-L1 can bind to the PD-1 on the surface of CD8+ T cells, inhibiting the activity of CD8+ T cells. This interaction can prevent the immune system from damaging normal tissues, but it can also be used by tumor cells to escape immune surveillance. Monoclonal antibodies that competitively bind to PD-L1 can relieve the immune function inhibition mediated by the binding of PD-1 and PD-L1. This can reactivate CD8+ T cells, triggering the human body's anti-tumor immune response ^[5]. Therefore, development of antibody drugs targeting PD-1 and PD-L1 is a hot area in tumor immunotherapy ^[5-7]. B6-h4-1BB/hPDL1 mice are TNFRSF9 and CD274 double humanized mouse models obtained by mating TNFRSF9 humanized mouse models (Catalog No. C001604) with CD274 humanized mouse models (Catalog No. C001235). They express human TNFRSF9 and CD274 genomic sequences under the control of mouse promoters. This model is a valuable tool for studying cancer immunotherapy. In addition, this model also provides a powerful preclinical research platform for evaluating the efficacy and mechanism of therapeutic drugs targeting TNFRSF9 and CD274.

Programmed cell death protein 1 (PDCD1/PD-1) is a member of the B7-CD28 costimulatory receptor family. It is an inhibitory receptor expressed on activated T cells and plays a role in regulating the function of effector T cells, including CD8+ T cells, and promoting the differentiation of CD4+ T cells into regulatory T cells. PD-1 is expressed in a variety of tumors and plays an important role in antitumor immunity. In addition, PD-1 is involved in the defense against autoimmune diseases and has inhibitory effects on antitumor and antimicrobial immunity ^[1]. Programmed cell death 1 ligand 1 (PD-L1), also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7H1), is an immune inhibitory receptor ligand. PD-L1 is a type I transmembrane protein with immunoglobulin V-like (IgV) and C-like (IgC) structural domains and is expressed by hematopoietic and non-hematopoietic cells, including T cells, B cells, and various types of tumor cells ^[2]. PD-L1 can bind to the PD-1 on the surface of CD8+ T cells, inhibiting the activity of CD8+ T cells. This interaction can prevent the immune system from damaging normal tissues, but it can also be used by tumor cells to escape immune surveillance. Monoclonal antibodies that competitively bind to PD-L1 can relieve the immune function inhibition mediated by the binding of PD-1 and PD-L1. This can reactivate CD8+ T cells, triggering the human body's anti-tumor immune response ^[3]. Therefore, development of antibody drugs targeting PD-1 and PD-L1 is a hot area in tumor immunotherapy ^[3-5]. The Vascular Endothelial Growth Factor (VEGF) family is a group of particular endothelial growth factors intimately associated with angiogenesis. These factors promote increased vascular permeability, extracellular matrix degeneration, vascular endothelial cell migration and proliferation, and are capable of stimulating angiogenesis and increasing the permeability of existing vessels. As such, they play a pivotal role in normal vascular development and wound healing. The VEGF family comprises VEGFA, VEGFB, VEGFC, VEGFD, VEGFE, and PLGF ^[6]. Of these, VEGFA is the most commonly targeted in research related to neovascular ophthalmic diseases due to its crucial role in the proliferation, migration, and formation of endothelial cell microvessels ^[7]. Overexpression of VEGFA in the eye can result in abnormal vascular growth and leakage, leading to various ophthalmic diseases such as Age-Related Macular Degeneration (AMD), Diabetic Retinopathy (DR), and corneal neovascularization ^[7-8]. The progression of solid tumors depends on vascularization and angiogenesis within malignant tissues, with VEGFA playing a crucial role among various pro-angiogenic factors. The VEGFA gene is upregulated in many known tumors, correlating with tumor staging and progression. Blocking VEGFA may lead to vascular network regression, thereby inhibiting tumor growth ^[9]. Thus, VEGFA is an important target for anti-angiogenic cancer therapies. B6-hPD-1/hPD-L1/hVEGFA mouse is a triple-gene humanized model generated by crossing B6-hPD-1/hPD-L1 mice (Catalog No.: I001202) with B6-hVEGFA mice (Catalog No.: C001555). This model serves as a valuable tool for research on cancer immunotherapy and can also be used for the screening, development, and preclinical evaluation of PD-1/PD-L1/VEGFA-targeted drugs.