PD-L1 VS PD-1

There are currently two main classes of immune drugs, PD-1 monoclonal antibodies and PD-L1 monoclonal antibodies. These two drugs are targeting the two endpoints of the same immune pathway, and the mechanisms seem to be the same. In fact, there are some differences between the two, whether in drug design, mechanism of action, and even drug resistance treatment.

Here, Creative Biolabs shares a comprehensive analysis of PD-1 and PD-L1 immune checkpoints, exploring the differences between PD-1 and PD-L1.

What are PD-1 and PD-L1?

Treatment that blocks the PD-1/PD-L1 pathway has become the focus of cancer immunotherapy. So, what exactly are the two and how are they really different? The table below lists some key information.

	PD-1	PD-L1
Definition	PD-1 is programmed death receptor 1, an immune checkpoint receptor expressed by activated T cells and an important immunosuppressive molecule.	PD-L1 is a ligand for PD-1.
Expression	PD-1 is expressed on the surface of T cells, B cells and other immune cells. However, PD-1 is expressed on the surface of T cells only after T cell activation.	PD-L1 is expressed on the surface of tumors and is involved in immune escape, as well as on the surface of antigen-presenting cells and vascular endothelial cells.
Function	PD-1 regulates the immune system and promotes self-tolerance by down-regulating the immune system's response to human cells and by suppressing T-cell inflammatory activity.	PD-L1 is associated with suppression of the immune system by transmitting inhibitory signals.

What is the Difference Between PD-L1 Inhibitors and PD-1 Inhibitors?

PD-1 monoclonal antibody and PD-L1 monoclonal antibody, the drugs used for cancer immunotherapy block the binding of PD-1 to PD-L1, restores T-cell tumor activity, activates T-cells, and kills tumor cells. What is the difference between these two?

Different drug structures
a. PD-1 inhibitors are mostly IgG4 antibodies, target cells are T cells, PD-1 inhibitors affect the function of immune T cells. IgG4 antibodies have poor structural stability, so almost all PD-1 inhibitors are modified to increase stability.
b. Most of the PD-L1 inhibitors are IgG1 antibodies, and the target cells are tumor cells, which are affected by PD-L1 inhibitors. IgG1 monoclonal antibody is the most commonly used monoclonal antibody, with a long half-life and good stability.
Different mechanisms of action
a. PD-1 inhibitors bind to PD-1 on the surface of T cells, blocking the binding of PD-1 and PD-L1/PD-L2, lifting the activation and proliferation inhibition of T cells, leaving tumor-specific T cells in an activated state, and restoring the killing function of T cells.
b. PD-L1 inhibitors simultaneously bind PD-L1 on the surface of tumor cells and antigen-presenting cells, with strong overall immune efficacy, restoring T-cell-mediated anti-tumor immunity without affecting the physiological function of PD-L2.

PD-1/PD-L1 is the immune checkpoint we are most familiar with at present. In recent years, immune checkpoint inhibitors represented by PD-1/PD-L1 inhibitors have made breakthrough progress in tumor immunotherapy. With continued research and innovation, Creative Biolabs provides research services to advance the drug development of PD-1/PD-L1 and other immune checkpoints.

References

Annika De Sousa Linhares, et al. Therapeutic PD-L1 antibodies are more effective than PD-1 antibodies in blocking PD-1/PD-L1 signaling. Sci Rep, 2019 Aug 7;9(1):11472.
Kim C Ohaegbulam, et al. Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway. Trends Mol Med, 2015 Jan;21(1):24-33.

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