Immune checkpoint-targeted therapy is producing unprecedented clinical results in various kind of cancer patients. Currently, researchers continue to identify an increasing number of immune checkpoints as novel targets for anti-tumor therapy. Co-engagement of multiple immune inhibitory receptors, known as combination immunotherapy, could potentially show better therapeutic outcomes compared with treatment of a single blockade. As always following the research highlight, Creative Biolabs currently offers the Magic™ dual immune checkpoint “humanized” mouse models that are specially designed for in vivo assay, including the humanized PD-L1/TIGIT dual immune checkpoint knock-in mice.
PD-L1 and TIGIT Immune Checkpoint Pathway
PD-L1 (Programmed death-ligand 1), also known as CD274 (cluster of differentiation 274) or B7-H1 (B7 homolog 1), is type 1 transmembrane protein expressed on the tumor cell surface, or on neighboring host immune cells in the tumor microenvironment. The expression of PD-L1 can be induced by tumor cell intrinsic signals and extrinsic signals. When bound to PD-1 on T-cell lymphocytes, PD-L1 negatively regulates the activity of T cells and other immune cells, and it exerts a wide range of immunoregulatory roles in T cells activation and tolerance.
T cell Ig and ITIM domain (TIGIT) is an inhibitory receptor that is expressed on activated T cells, Tregs, and NK cells and could produce negative signals within the T-cell, abrogating the immune response. The ligand for TIGIT is known as CD155, which is alternatively called PVR (Polio Virus Receptor). And CD155 is considered binding to TIGIT with high affinity, while PVRL2 (Nectin2 or CD112) binds to TIGIT with a weaker binding capacity. When TIGIT is bound to CD155, it transmits an inhibitory signal by recruiting the SHP1 phosphatase to the membrane through its ITIM domain that subsequently deactivates numerous proteins involved in T-cell effector functions.
Combination of Anti-PD-L1 and Anti-TIGIT Immunotherapies
It has been known that several immune checkpoint inhibitors have the capacity to enhance T cell responses when combined with PD-L1 pathway blockade. Antibody coblockade of TIGIT and PD-L1 synergistically and specifically enhanced CD8(+) T cell effector function, resulting in significant tumor inhibition. Also, a study found that the TIGIT together with PD-1 regulate the expansion and function of TA-specific CD8+ T cells and CD8+TILs in melanoma patients. These indicate that the use of dual PD-L1 and TIGIT blockade will stimulate potent antitumor CD8+ T cells responses in patients with advanced melanoma.
Development of Humanized PD-L1/TIGIT Dual Immune Checkpoint Knock-In Mice
The outcomes of numerous clinical trials support the strategy of combination immunotherapy. For instance, therapies of blocking with PD-L1 monoclonal antibodies (mAbs), which have shown positive clinical treatment effect, are now widely been evaluated in combination with novel mAbs that targeted other immune checkpoint receptors. With upgraded transgenic technology, scientists in Creative Biolabs is able to generate dual “humanized” immune checkpoint knock-in mouse models with comprehensive validation and immune-profiling data, including the PD-L1/TIGIT. We also provide the most professional technical support to assist you in your drug discovery research. Please feel free to contact us for more detailed information.
Creative Biolabs also offers other various Humanized Mouse Models you may be interested in:
For Research Use Only.
