CTLA-4: Two Sides of a Coin
Immuno-Oncology has revolutionized the way we treat cancer. Cell therapy and immune checkpoint inhibitor therapy can lead to durable cancer remission. Immune checkpoint inhibitor therapy removes the inhibitory signals of T cell activation, allowing the immune system to mount an effective anti-tumor response1. Antibodies against Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4), Programmed Death-1 (PD-1), and Programmed Death Ligand-1 (PD-L1) successfully treat many cancers, including melanomas, carcinomas, and non-small cell lung cancer.
CTLA-4 plays a well-described immunosuppressive role in the immune system1, specifically in the interaction between T cells and antigen-presenting cells (APCs). CTLA-4 keeps immune responses within a desired physiological range to protect against autoimmunity. CTLA-4 expression at the immunological synapse is upregulated in response to T Cell Receptor (TCR) stimulation, peaking in 2-3 days. It has a higher affinity and is a more avid receptor for B7-1 and B7-2 than the co-stimulatory CD-28 (Figure 1). By outcompeting CD-28, CTLA-4 diminishes TCR signaling and attenuates T Cell activation. Tumors take advantage of the immunosuppressive role of CTLA-4 to evade the immune system.
By targeting checkpoint proteins such as CTLA-4 with antibodies, investigators can block CTLA-4’s coinhibitory activities and stimulate T cell responses that attack tumors. CTLA-4 was the first checkpoint inhibitor approved for the treatment of cancer by the FDA in 20111.
Given CTLA-4’s immunosuppressive role, it is no surprise then that immune checkpoint inhibitor therapy can be associated with immune-related adverse events (ir-AEs) that affect the skin, liver, gastrointestinal (GI) system, and endocrine systems2. A variety of autoimmune side effects are possible, including skin rash, diarrhea, thyroiditis, and hepatitis. For example, the side effects triggered by CTLA-4 checkpoint therapy for metastatic melanoma typically follow a stereotypical course2, with cutaneous side effects occurring after 3-4 weeks, while GI and hepatic side effects occur after 6-7 weeks, and endocrine side effects occur after nine weeks typically.
Choose Quantikine™ ELISAs for Your Immuno-Oncology Research
The R&D Systems Human Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) High Sensitivity ELISA is sensitive, specific, and provides high-quality data so you don’t have to worry about repeating experiments. We have decades of experience manufacturing ELISAs. Count on our ELISAs for consistent and reproducible data. Our ELISAs are regularly tested for lot-to-lot consistency, precision, recovery, and linearity.
Explore the technical details:
Real-World Human CTLA-4 Quantikine HS ELISA Kit Data
Figure 1 quantifies CTLA-4 in serum samples from cancer patients and healthy individuals. Soluble CTLA-4 is elevated in serum from a variety of autoimmune diseases3. In figure 2 we quantify CTLA-4 from a broad range of autoimmune diseases including ulcerative colitis and rheumatoid arthritis.
Serum CTLA-4 in Cancer
Figure 1. The Quantikine CTLA-4 HS ELISA reliably quantifies CTLA-4 in cancer patients and healthy controls.
Serum CTLA-4 in Autoimmune Disease
Figure 2. The Quantikine CTLA-4 HS ELISA detects CTLA-4 in serum from patients with autoimmune disease. Healthy data is identical to that in figure 1.
Related Immune Checkpoint Immunoassays
Choose R&D SystemsTM Luminex® assays to maximize multiplexing capacity and flexibility while maintaining specificity. Leverage QuantikineTM ELISAs, the most trusted name in the market to for accurate and reproducible results. QuicKit ELISAs offer Quantikine-quality data in 90 minutes or less. DuoSet ELISAs are a cost-effect alternative to buying separate antibodies and proteins and optimizing your own assay. Finally, Simple Plex automated immunoassays afford you a higher level of precision to your workflow, getting you data in 90 minutes or less.
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1. Wei, S. C. et al (2018) Fundamental Mechanism of Immune Checkpoint Therapy. Cancer Discov. 8: 1069 PMID: 30115704
2. Kahler, K. C. et al (2015) Management of side effects of immune checkpoint blockade by anti-CTLA-4 and anti-PD-1 antibodies in metastatic melanoma. J Dtsch Dermatol Ges. 16: 662 PMID: 27373241
3. Simone, R. et al (2014) The Soluble Form of CTLA-4 of Patients With Autoimmune Diseases Regulates T Cell Responses. Biomed Res. Int. 2014: 215763 PMID: 24605322