The therapy of using monoclonal antibodies against inhibitory receptors on immune cells, termed immune-checkpoint blockade, for the treatment of human cancer has gained a great deal of attention among clinicians, scientists, and patients. Checkpoint inhibitors have shown satisfactory efficacy in treatment for various human cancer. Immune checkpoint antibodies that augment the programmed cell death protein 1 (PD-1)/PD-L1 immune checkpoint pathway have shown antitumor activity across multiple malignancies. As a world leader in the industry of drug discovery, Creative Biolabs has successfully established a serious of Magic™ “humanized” animal models and can provide specialty humanized PD-1/PD-L1 dual immune checkpoint knock-in mice for our clients all over the world.

PD-1/PD-L1 Signaling Pathway

In recent years, cancer immunotherapy and particularly monoclonal antibodies blocking the inhibitory programmed cell death 1 pathway (PD-1/PD-L1) have made a significant impact on the treatment of cancer patients. Programmed death-1 (PD-1) is a member of the CD28 family, which is a 50-55 kDa type I transmembrane receptor. PD-1 is involved in the regulation of T-cell activation and is expressed on T cells, B cells, and myeloid cells.

The ligand for PD1, PD ligand 1 (PD-L1) is commonly expressed on the surface of dendritic cells or macrophages and have been identified to be a co-stimulatory molecule. Programmed cell death 1 ligand 1 (PD-L1), also known as cluster of differentiation (CD274) or B7 homolog 1 (B7-H1), is a member of the B7 family that modulates activation or inhibition of the PD-1 receptor. In humans, PD-L1 is usually expressed on a number of immune cell types including activated and anergic/exhausted T-cells, on naive and activated B-cells, as well as on monocytes, mast cells and myeloid dendritic cells (DC).

Combination of Anti-PD-L1 and Anti-PD-L1 Immunotherapies

PD-1/PD-L1 inhibition has indicated remarkable anti-tumor activity, including durable responses for several ways, in a broad range of solid and hematological malignancies, resulting in regulatory approval of an increasing list of agents in a growing number of cancers.

Magic™ Humanized PD-1/PD-L1 Dual Immune Checkpoint Knock-In Mice Fig.1. Mechanism of anti-programmed death 1 (PD-1) receptor and anti-programmed death ligand 1 (PD-L1)/L2 inhibitors mediated cancer immunotherapy. Antigen-presenting cells (APCs) bind to antigen (Ag) that released from tumor cells and T cells to activate T-cell receptor (TCR) and MHC binding. PD-L1 of tumor stroma interacts with PD-1 of T cells to suppress the T-cell mediated tumor cytotoxicity. Tumor associated macrophage (TAM), myeloid derived suppressor cells (MDSC) has crucial role in PD-1/PD-L1 mediated tumor immunosuppression. (Ohaegbulam et al., 2015)

Development of Humanized PD-1/PD-L1 Dual Immune Checkpoint Knock-In Mice

Checkpoint blockade is a promising immunotherapy approach to block the ability of certain proteins, called immune checkpoint proteins, which limit the duration and strength of immune responses. Recently, checkpoint blockade therapies have achieved significant clinical advances, resulting in durable clinical responses and long-term remission in a group of treated patients. It has been reported that the combination immunotherapy of different immune checkpoint inhibitors offers promising future cancer treatment. With advanced technology and years of experience, Creative Biolabs has successfully launched a group of well-characterized Magic™ “humanized” immune checkpoint knock-in mouse models, particularly for the humanized PD-1/PD-L1 dual immune checkpoint knock-in mice. Our scientists are willing to assist you in your studies of anti-tumor immunotherapies. Please feel free to contact us for more detailed information.

Creative Biolabs also offers other various Humanized Mouse Models you may be interested in:

Reference

  1. Ohaegbulam, K. C.; et al. Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway. Trends in Molecular Medicine. 2015, 21(1):24-33.

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