Technology/ Title:MAP4K3 is a therapeutic target for cancer and IL-17A-mediated autoimmune disease

Technology Type:

Contact Person

Tse-Hua Tan
Founding Director and Distinguished Investigator, Immunology Research Center, National Health Research Institutes, Taiwan
+886-37-246166 ext. 37601

Technology Description

Our team has identified MAP4K3 (GLK), MAP4K1 (HPK1), and MAP4K4 (HGK) in the 1990s.

We reported that MAP4K3 (GLK) overexpression is correlated with human autoimmune diseases and cancer recurrence. Using MAP4K3-deficient and MAP4K3 transgenic mice, we demonstrated that MAP4K3 overexpression selectively induces IL-17A overproduction through AhR-RORγt complex in T cells, leading to autoimmune responses. Our findings indicate that MAP4K3 is a therapeutic target for autoimmune disease, cancer, and IL-17A-mediated disease. We further showed proof of concept by treatment of GLK inhibitors in mouse disease models.

Our team also demonstrated that HPK1 (MAP4K1) is a negative regulator of T-cell activation in 2007. Based on our finding, at least 10 companies have filed 23 patents on HPK1 inhibitors (plus anti-PD1) for cancer immunotherapy.

Intellectual Property


MAP4K3 as a biomarker and therapeutic target for autoimmune disease, cancer, inflammation and IL-17-associated disease.

1. US patent (US8846311, 2014/09/30)
2. Taiwan patent (TWI510629, 2015/12/01)
3. Europe patent (EP2732045, 2017/07/19, Nations registered: Germany, French, UK, Switzland)
4. China patent (CN103827310, 2017/09/22)
5. Japan patent (JP6351503, 2018/06/15)
6. Korea patent (KR101640326, 2016/07/11)

The AhR-RORγt complex as a biomarker and therapeutic target for autoimmune disease and IL-17-associated disease. (U.S. provisional patent application, 2018)

Key Publications:

Chuang, H.C., J.L. Lan, D.Y. Chen, C.Y. Yang, Y.M. Chen, J.P. Li, C.Y. Huang, P.E. Liu, X. Wang, and T.-H. Tan. 2011. The kinase GLK controls autoimmunity and NF-κB signaling by activating the kinase PKC-θ in T cells. Nature Immunology, 12:1113-1118.

Chuang HC, CY Tsai, CH Hsueh and T.-H. Tan. 2018. GLK-IKKβ signaling induces dimerization and translocation of the AhR-RORγt complex in IL-17A induction and autoimmune disease. Science Advances, 4: eaat5401.

Shui, J.-W., J.S. Boomer, J. Han, J. Xu, G.A. Dement, G. Zhou, and T.-H. Tan. 2007. HPK1 negatively regulates T-cell receptor signaling and T-cell-mediated immune responses. Nature Immunology, 8:84-91.

Business Opportunity

Technology transfer (license out) and co-development of novel MAP4K inhibitors and biomarkers for cancer and IL-17A-mediated autoimmune disease.

1. Small-molecule inhibitors of MAP4K3 (GLK) should be cost-effective therapeutic drugs for cancer and IL-17A-mediated autoimmune disease.

2. Screening MAP4K3 (GLK) inhibitors should also help development of HPK1 (MAP4K1) inhibitors.