Recent advances in the field of tumor immunology and immunotherapy, the recognition of the produced immune checkpoint proteins can be blocked by human antibodies. The immune checkpoint pathway contains costimulatory and inhibitory proteins. Co-stimulatory receptor switching signals promote immune function against pathogens. Inhibitory receptors, on the other hand, negatively regulate T cell activation to prevent excessive inflammatory responses. Immunomodulatory antibodies directed against cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) have shown great promise in the treatment of melanoma and other types of tumors.
Figure 1. Complex Interactions between the CTLA-4/CD28 and PD-1 Families of Receptors and Ligands.( Suzanne L. Cancer Cell. et al. 2015)
These agents are often called "checkpoint inhibitors" because they block negative regulators of normal T cell immunity. Many other immune checkpoint approaches, which may be targets for new therapies, have been identified and are currently being developed for clinical trials. We provide comprehensive immune checkpoint proteins and antibodies to support immune checkpoint blocking studies. These products show consistency and excellent performance in a variety of testing experiments.
Summary of key immune checkpoint goals
T cell activation is usually self-limiting because activated T cells express a receptor that mediates PD-1 (also known as PDCD-1), which mediates inhibitory signals from antigen-presenting cells. PD-1 can bind two different but related ligands PD-L1 and PD-L2. Upon binding to any of these ligands, the signal produced by PD-1 reduces TCR-mediated proliferation and cytokine production. Increased PDL-1 expression is associated with many murine and human cancers and can be further up-regulated after IFN-γ stimulation. Therefore, PD-L1 may play an important role in tumor immune escape.
DR3/TNFRSF25 is a member of the TNF receptor superfamily. This receptor is preferentially expressed in lymphocyte-rich tissues, and it may play a role in regulating lymphocyte homeostasis. The only known ligand for DR3 is the TNF superfamily member TL1A (TNF-like cytokine 1A, TNFSF15). Signaling of this receptor is mediated by a variety of adaptor proteins containing death domains.
CTLA4 is a member of the immunoglobulin superfamily and encodes a protein that transmits inhibitory signals to T cells. Mutations in this gene have been linked to insulin-dependent diabetes, Graves' disease, Hashimoto's thyroiditis, celiac disease, systemic lupus erythematosus, thyroid-related orbital disease, and other autoimmune diseases. CD80 (B7-1) and CD86 (B7-2) are ligands for key T-cell co-stimulatory molecules CD28 and inhibitory receptor CTLA-4 (CD152). Both B7 molecules are expressed on professional antigen-presenting cells and are critical for T cell activation. The differences in the capacity of CD80 and CD86 have not been fully elucidated; the results of existing studies conflict with their respective roles in initiating or maintaining T-cell immune responses.
Figure 2. Two General Mechanisms for Expression of Checkpoint Ligands in the TME. ( Suzanne L. Cancer Cell. et al. 2015)
Immune Checkpoint pathway includes Costimulatory Proteins and Coinhibitory Proteins. Co-stimulatory proteins can transmit signals to promote an immune response to pathogens. In contrast, co-suppressors negatively regulate T lymphocyte activity and prevent excessive inflammatory responses. In recent years, immune checkpoint proteins have attracted much attention because of their important role in tumorigenesis and development. In general, tumor cells can escape from the immune system by blocking the immune checkpoint pathway. Therefore, researchers believe that regulating immune checkpoint pathways can reactivate the immune system to fight tumors. It is worth mentioning that anti-CTLA4 and anti-PD1 monoclonal drugs have shown good results in clinical trials of a variety of malignancies. At the same time, researchers are also developing antibody drugs targeting other checkpoint proteins, in order to find more Good way to treat tumors.