Immune checkpoints refer to proteins that act as T cell receptor (TCR) co-signaling partners which deliver either positive or negative signals to T lymphocytes. Blocking the actions of the immune checkpoint receptors can produce a potent anti-tumor response, and it has been regarded as one of the most promising approaches to activating therapeutic antitumor immunity. In view of the clinical success of inhibitory immune checkpoint blockade (CTLA-4, PD-1, and PD-L1), monoclonal antibodies against CD276 appear to be an attractive therapeutic strategy. Scientists in Creative Biolabs spare no efforts developing variety of well-characterized Magic™ “humanized” animal models, which can provide you with humanized immune checkpoint knock-in mouse models including humanized CD276 knock-in mouse and professional technical support.

CD276 Immune Checkpoint Pathway

CD276 (Cluster of Differentiation 276), also known as B7-H3, is a type I transmembrane protein as well as an important immune checkpoint molecule belonging to the B7 ligand families. CD276 plays a vital role in the inhibitions of T-cell function, which provide T-cell costimulation and coinhibition, regulating T-cell activation and tolerance, exhaustion and effector function, differentiation, and memory generation. CD276 is constitutively expressed on nonimmune resting fibroblasts, endothelial cells (EC), osteoblasts, and amniotic fluid stem cells. Furthermore, CD276 would be induced to express on immune cells such as antigen presenting cells (APCs) and dendritic cells (DCs). CD276 is also detected on natural killer (NK) cells, B cells, and a minor population of T cells following PMA/ionomycin stimulation Significantly, CD276 is highly overexpressed on a wide range of human solid cancers and often correlates with both negative prognosis and poor clinical outcome in patients.

The Significance of CD276 Immune Checkpoint Pathway

Although the definition of its ligand and the nature of its signaling remains controversial, numerous literature suggests that CD276 plays a crucial role in T cell-mediated adaptive immunity. The CD276 pathway is considered to have a dual role in contributing to the regulation of innate immune responses. One study shows that neuroblastoma cells express CD276 on their cell surface, which protect them from NK cell-mediated lysis. Another study suggests that CD276 costimulates innate immunity by augmenting proinflammatory cytokines release from LPS-stimulated monocytes/macrophages, in both a Toll-like receptor 4- and 2–dependent manner.

Magic™ Humanized CD276 Immune Checkpoint Knock-In MiceFig.1. Human cancer immunotherapy strategies targeting B7-H3 (CD276). (Picarda, et al., 2016)

The Clinical Application of CD276

Nowadays, therapeutic approaches in targeting CD276 appear to be a promising therapeutic strategy worthy of development. An unconventional mAb against CD276 with antibody-dependent cell-mediated cytotoxicity is currently being evaluated in phase I clinical trial and has shown encouraging preliminary results. Accordingly, using the KI mouse model to make a better understanding of the CD276 signaling pathway will surely help to further optimize associated cancer immunotherapies.

Development of Humanized CD73 Immune Checkpoint Knock-In Mice

Compared to the ordinary mouse, the Magic™ mouse models in Creative Biolabs have many advantageous features: the models carry a 100% human CD276 gene which eliminates the human-to-mouse deviation related to drug targets; meanwhile, unlike other humanized mice, immune checkpoint KI mouse maintains an intact immune system that assures better predict drug efficacy and side effects. As a world leader in the industry of animal model and drug discovery, we now guarantee the high knock-in efficiency with no other genes compromised. 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. Picarda, E.; et al. Molecular pathways: Targeting B7-H3 (CD276) for human cancer immunotherapy. Clinical Cancer Research. 2016, 22(14):3425-3431.

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