IL-2 & IL-15 Pathways: Charting a Bold Frontier in Oncology and Autoimmune Therapies with Biocytogen’s Advanced Mouse Models
The immune system is a complex network orchestrated by cytokines, which act as critical mediators of immune responses. Among them, IL-2 and IL-15, key members of the cytokine receptor γ-chain family, hold unique potential in tumor and autoimmune therapies. These type I four-helix bundle cytokines share several biological activities, including promoting the proliferation and activation of T cells and NK cells, inducing immunoglobulin synthesis in B cells, and supporting the differentiation of cytotoxic effector cells.
IL-2 and IL-15 function as the immune system’s “dual coaches.” IL-2 manages both the “offense” (effector T cells and NK cells) and the “defense” (Treg cells) teams, ensuring a fine-tuned balance between immune activation and regulation (Boyman & Sprent, 2012). In contrast, IL-15 focuses on preparing the “long-term strike force” (memory CD8+ T cells and NK cells) to maintain sustained readiness for extended challenges, particularly in combating tumors and infections (Zhang et al., 1998, Schluns, Klonowski, & Lefrançois, 2004).
IL-2: The Balancing Act
Primarily secreted by activated T cells, IL-2 binds to its three-part receptor complex (IL-2Rα/CD25, IL-2Rβ/CD122, IL-2Rγ/CD123), activating key signaling pathways such as JAK-STAT, PI3K/AKT, and MAPK/ERK to promote the proliferation of T cells and NK cells. In addition to stimulating effector T cells, IL-2 plays a crucial role in expanding regulatory T cells (Tregs), thereby maintaining a dynamic balance between immune activation and suppression (Yang & Lundqvist, 2020). At low doses, IL-2 preferentially binds to the high-affinity IL-2Rβγ receptor, activating Treg cells and significantly improving immune tolerance in patients with autoimmune diseases. Conversely, at high doses, IL-2, after saturating Treg cells, engages receptors with moderate affinity, boosting the cytotoxicity of CD8+ T cells and NK cells.

IL-15: Sustained Immune Readiness
IL-15 is secreted by monocytes and macrophages, with its signaling relying on trans-presentation through IL-15Rα. While IL-15 shares receptor chains (IL-2Rβ and IL-2Rγ) with IL-2, leading to similar signaling pathways, it exhibits distinct biological properties. IL-15 primarily enhances the activity of memory CD8+ T cells and activates NK cell cytotoxicity, while exerting minimal effects on Treg cells. Unlike IL-2, IL-15 supports long-term immune surveillance, making it particularly advantageous for cancer immunotherapy and infectious disease treatments (Waldmann, 2015). Moreover, its relatively low toxicity profile positions IL-15 as an ideal candidate for developing long-acting immune therapeutics.

Biocytogen has developed a series of humanized and severely immunodeficient mice targeting IL-2, IL-15, and their signaling pathways. These models provide robust support for preclinical drug research and drive advancements in oncology and autoimmune therapy development.
Case Study: B-hIL2RB/hIL2RG Mice

Case Study: B-hIL15/hIL15RA Mice

Case Study: B-hIL2RB/hIL2RG/hIL15/hIL15RA Mice

The experiment was verified by the partner, and the drugs used belong to the client. MDNA11 analog does not bind to human IL-2RA but exhibits higher affinity for human IL-2RB.
IL-2 and IL-15 Related Mouse Models at Biocytogen
Contact us to learn more about Biocytogen’s humanized and severely immunodeficient mice targeting IL-2, IL-15, and their receptor pathways!
References
Boyman, Onur, and Jonathan Sprent. “The role of interleukin-2 during homeostasis and activation of the immune system.” Nature Reviews Immunology 12.3 (2012): 180-190.
Zhang, Xiaohong, et al. “Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15.” Immunity 8.5 (1998): 591-599.
Schluns, Kimberly S., Kimberly D. Klonowski, and Leo Lefrançois. “Transregulation of memory CD8 T-cell proliferation by IL-15Rα+ bone marrow–derived cells.” Blood 103.3 (2004): 988-994.
Yang, Ying, and Andreas Lundqvist. “Immunomodulatory effects of IL-2 and IL-15; implications for cancer immunotherapy.” Cancers 12.12 (2020): 3586.
Holcomb, Erin A., and Weiping Zou. “A forced marriage of IL-2 and PD-1 antibody nurtures tumor-infiltrating T cells.” The Journal of Clinical Investigation 132.3 (2022).
Waldmann, Thomas A. “The shared and contrasting roles of IL2 and IL15 in the life and death of normal and neoplastic lymphocytes: implications for cancer therapy.” Cancer immunology research 3.3 (2015): 219-227.