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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.

B7-1 binds to CD28 or CTLA-4 to deliver a co-stimulatory or co-inhibitory signal that regulates T cell activitation.

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:

CTLA-4 precision | CTLA-4 recovery | CTLA-4 Linearity | About CTLA-4

Find Out More About CTLA-4 and Other Checkpoint Proteins

Explore Research Grade CTLA-4 Biosimilar Antibodies

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  levels in cancer patients measured with Quantikine High Sensitivity CTLA-4 ELISA

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  levels in patients with autoimmune disease measured with Quantikine High Sensitivity CTLA-4 ELISA

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

CTLA-4     Human CTLA-4 Quantikine High Sensitivity ELISA Kit  | CTLA-4 Simple PlexTM Immunoassay

PD1           PD-1 Quantikine ELISA  |  PD-1 DuoSetTM ELISA  |  PD-1 QuicKitTM ELISA

PD-L1        PD-L1 Quantikine ELISA  |  PD-L1 DuoSet ELISA  |  PD-L1 Simple Plex Immunoassay  |  PD-L1 Luminex Performance Assay

Other Resources

                    Explore B7-CD28 Families of Immune Checkpoint Proteins

                    Explore Immune Checkpoint Proteins

                    Immunoassays for Immuno-Oncology

                    ELISA Kits

                    Custom ELISA Services

                    Luminex Assays and Panels

                    Simple Plex Assays

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Current and Emerging Immune Checkpoint Targets for Immuno-Oncology Research



Request this ebook to see some of the current and emerging immune checkpoint molecules that are being investigated as potential targets for cancer immunotherapy. This ebook also details products that we offer for studying these molecules.