Figure 2. Key ligand-receptor interactions between T cells and APCs. T cell activation follows after TCR recognition of MHC with co-stimulatory signal from B7-1 binding with CD28. T cells are deactivated if MHC-TCR recognition is followed by co-inhibitory signal from B7-1 binding with CTLA-4 or PD-L1 binding with PD-1.

However, we now know that cancer cells can express high levels of some immune checkpoint proteins, essentially exploiting T cell suppressive effects and evading the immune response for tumor survival³. As we learned earlier, antibodies can target immune checkpoint proteins and block binding at T cell-tumor cell interfaces (Fig 3), freeing T cells to attack tumor cells. Antibodies now designed to target checkpoint proteins, called immune checkpoint inhibitors (ICIs) (Fig 3), are the subject for numerous drug discovery and development enterprises and considered among the most rapidly emerging immunotherapies⁴.

Figure 3. Illustration showing checkpoint proteins PD-L1 expressed on tumor cells and PD-1 on T cells. Interaction between PD-L1 and PD-1 prevents T cells from destroying tumor cells (top, Before). Using immune checkpoint inhibitors to either PD-1 or PD-L1 allows the T cells to kill the tumor cells (bottom, After).

BioLegend is committed to empowering cancer research and advancements toward novel immunotherapies by providing trusted, expertly-crafted resources. Our portfolio includes Avi-tag biotinylated proteins, which offer consistent labeling, uniform orientation of the protein, equivalent bioactivity to that of non-biotinylated proteins, and lot-to-lot consistency. Learn about biofunctional recombinant proteins and functional antibodies we offer for immune checkpoints being evaluated as immuno-oncology targets.

Researchers can also test strategies for stimulating anti-cancer immune responses with in vivo and ex vivo models using our bioactive GoInVivo™ antibodies. These antibodies are designed to target immune checkpoint markers, validated by functional assay, and competitively priced for bulk purchase.

Finally, the ability to accurately quantify expression levels of checkpoint molecules is critical to ongoing biomedical research with the goal of developing potential immunotherapeutic interventions. Learn about our LEGENDplex™ Human Immune Checkpoint Panel 1, a flow-based multiplex assay that allows for the simultaneous quantification of 12 key immune checkpoint biomarkers (sCD25 (IL-2Ra), 4-1BB, sCD27, B7.2 (CD86), Free Active TGF-β1, CTLA-4, PD-L1, PD-L2, PD-1, Tim-3, LAG-3, and Galectin-9). The panel has been validated for use on cell culture supernatant, serum, and plasma samples (Fig 4).

Figure 4. Serum and EDTA plasma samples were obtained from healthy donors and patients with confirmed breast and lung cancer. Serum and plasma samples were run neat and analytes analyzed using LEGENDplex Human Immune Checkpoint Panel 1 (12-plex).

The growing field of immunotherapy has revolutionized cancer treatment by boosting the body’s own immune system to target and eliminate malignant tumors⁸. Along with ICIs, bispecific antibodies and CAR-T cells are considered the most promising immunotherapies⁹. In this blog, we focused on immune checkpoints; cell surface molecules that regulate T cell functions and activities, but which can also be exploited by tumor cells to evade immune control. That discovery triggered intense research into ICIs that have now transitioned to the clinic and are considered standard treatment for a number of cancers. However, there are still unmet medical needs and our scientists are ready to support R&D that will lead to the next generation of innovative treatments.

References

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