Creative Biolabs currently provides unique transgenic mice/rats based on our Magic™ therapeutic antibody discovery platform. With our state-of-the-art gene editing techniques, we have obtained not only transgenic mice with the human immune system or secreting human antibodies but also immune checkpoint humanized mice. In particular, we now offer specialty human PD-1 and PD-L1 immune checkpoint knock-in mice to our worldwide clients.

Programmed death ligand 1 (PD-L1, also called B7-H1) is an immune checkpoint expressed on the tumor cell surface, or on neighboring host immune cells in the tumor microenvironment. It binds to PD-1 on T-cell lymphocytes, negatively regulates the activity of T cells and other immune cells. As the important role of T-lymphocytes in mediating acquired anti-tumor immunity, expression of PD-L1 in the tumor microenvironment can significantly inhibit the function of tumor-infiltrating T cells and initiate anti-immunity responses to escape immune surveillance.

Simplified illustration of the complex interaction between PD-1 and PD-L1 Fig.1 Simplified illustration of the complex interaction between PD-1 and PD-L1 (Hartkopf et al. 2016)

PD-L1 is broadly and variably expressed in a wide range of malignancies and blockade of the PD-L1 has great potential in overall survival benefits in many cancers, including lung cancer, melanoma, renal cell carcinoma, and urothelial carcinoma. PD-L1 expression can be induced by tumor cell intrinsic signals and extrinsic signals. For intrinsic signals, PD-L1 expression can be driven by the activation of protein kinase B (PKB), activator of transcription 3 (STAT3) pathways, activation of KRAS signaling pathway and the activation of EGFR pathway. Besides tumor cell intrinsic signals, PD-L1 expression can also be induced by extrinsic signals. Interferon-γ secreted by the infiltrated immune cells was required for PD-L1 induction. Atezolizumab (MPDL3280A), Avelumab (MSB0010718C) and Durvalumab (MEDI4736) are three humanized monoclonal antibodies that bind to PD-L1. Clinical trials of using these three antibodies directed against PD-L1 demonstrated striking therapeutic outcomes.

Development of PD-L1 Immune Checkpoint Knock-In Mice

Magic™ Humanized PD-L1 Immune Checkpoint Knock-In Mice

In vivo oncology assays are usually explored in human tumor xenografts growing in immunodeficient mice. However, as immunodeficient mice lack a human immune system, this approach is inadequate to test immunotherapy. Creative Biolabs has developed human PD-L1 immune checkpoint knock-in mice as a highly efficient model for evaluation of the in vivo efficacy of anti-PD-L1 antibodies. The uncompromised immune system of the mice, in contrast to immunodeficient models, is especially advantageous in immune effector function evaluation and side effect prediction. It has been proven in previous studies that this model is more accurate and predictive, which can ensure you more confidence in prior to human trials.

Meanwhile, we can also provide a broad range of immune checkpoint mouse models, including but not limited to:

We now proudly launch other various Humanized Mouse Models for choice. Please feel free to contact us for more details.

References

  1. Xu W, Jiang H, Gao J, et al. (2014) “The upregulation of immune checkpoint ligand PD-L1 in tumour microenvironment.” Scand J Immunol 80(1):71-72. doi: 10.1111/sji.12177.
  2. Hartkopf A D, Taran F A, Wallwiener M, et al. (2016) “PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer.” Breast Care 11:385-390.
  3. Al-Ahmadie H (2016) “PD-L1 expression in penile cancer: a new frontier for immune checkpoint inhibitors?” Ann Oncol 27 (9): 1658-1659.

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