IL-2 has been regarded as promising cancer therapeutic with a long history. It is capable of eliciting complete and durable remissions in patients with metastatic renal cell carcinoma and metastatic melanoma. IL-2 mediates its immune-enhancing effect through either a low-affinity dimeric and/or a high-affinity trimeric IL-2 receptor (IL-2R). IL-2R is composed of three subunits IL-2Rα (CD25), IL-2Rβ (CD122), and IL-2Rγ (CD132). The dimeric IL-2R consists of CD122 and CD132, whereas the trimeric IL-2R comprises an additional component, CD25, which increases the affinity for its ligand.
IL-2 is considered the first immunotherapy proven to be effective in human cancer in 1984. However, IL-2 has certain limitations because of its toxicity and pleiotropy. IL-2R agonists have been developed to potentiate and prolong IL-2 antitumor effects, allowing lower doses and decreased toxicities. Furthermore, IL-2R agonists could also enhance other forms of immunotherapy without the associated toxicity caused by IL-2.
IL-2Rαβγ trimeric complex shows the highest binding affinity to IL-2. The binding of IL-2 to the IL-2Rβγ or IL-2Rαβγ complex leads to the activation of multiple signaling pathways. The initial signal transduction involves the recruitment of Janus family tyrosine kinases (JAK1 and JAK3) to the cytoplasmic domains of IL-2Rβγ or IL-2Rαβγ. The activation of JAK kinases causes the recruitment and phosphorylation of signal transducer and activator of transcription 1 (STAT1), STAT3, STAT5A, and STAT5B. Then, three major downstream signaling pathways are activated, including the STAT signaling pathway, PI3K-AKT signaling pathway, and MAPK signaling pathway.
For many years, IL-2 related drug has been successfully used as a cancer treatment modality. IL-2 drug was also the first therapy regimen that demonstrated that stimulated T cells could eradicate large, invasive, and vascularized tumors in humans. Besides, some drugs have been developed and tested in solid tumors, including melanoma, non-small cell lung carcinoma (NSCLC), and breast cancer.
IL-2/IL-2R plays a critical role in activating the immune system that could be a useful way to eradicate cancer. With our advanced technology and abundant experience, Creative Biolabs offers high-quality customized service covering the entire drug development projects for IL-2/IL-2R. We provide the following services for our worldwide customers. For any questions, please feel free to contact us for more information.
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