Research Area

New immune checkpoints and immunotherapies: from discoveries to clinical trials.

Team Description

The Zang lab has made numerous important contributions to the fields of immune checkpoint and immunotherapy, including discovery of 3 (B7x, HHLA2, TMIGD2) out of 13 members of the B7 and CD28 families (major immune checkpoints), identification of the HHLA2-KIR3DL3 immunosuppressive pathway, identification of the HHLA2-TMIGD2 immunostimulatory pathway, demonstration of the biology and therapeutic potential of the KIR2DL5-PVR pathway, characterization of new mechanisms and structures of other immune checkpoints such as Tim-3, B7-H3, ICOS, PD-L1/PD-1, BTNL2, etc., and development of novel immunotherapies. Two novel immune checkpoint inhibitors from the Zang lab is currently in several phase II and phase I clinical trials in patients with advanced solid tumors and recurrent/refractory hematologic malignancies.

Team Members

Christopher Nishimura
Marc Pulanco
Devin Corrigan

Team Show

Publications

Pulanco MC, Madsen AT, Tanwar A, Corrigoan DT, Zang X. Recent advancements in the B7/CD28 immune checkpoint families: New biology and clinical therapeutic strategies. Cellular & Molecular Immunology, Apr 17. doi: 10.1038/s41423-023-01019-8, 2023.

Ren X, Peng M, Xing P, Wei Y, Galbo PM, Corrigan D, Wang H, Su Y, Dong X, Sun Q, Li Y, Zhang X, Edelmann W, Zheng D, Zang X. Blockade of the immunosuppressive KIR2DL5-PVR pathway elicits potent human NK cell-mediated anti-tumor immunity. Journal of Clinical Investigation, 132:e163620, 2022.

John P, Pulanco MC, Galbo PM, Wei Y, Ohaegbulam KC, Zheng D, Zang X. The immune checkpoint B7x expands tumor-infiltrating Tregs and promotes resistance to anti-CTLA-4 therapy. Nature Communications, 13:2506. doi: 10.1038/s41467-022-30143-8, 2022.

Picarda E, Galbo PM, Zong H, Rajan MR, Wallenius V, Zheng D, Borgeson E, Singh R, Pessin J, Zang X. The immune checkpoint B7-H3 (CD276) regulates adipocyte progenitor metabolism and obesity development. Science Advances, 8: eabm7012, 2022.

Wei Y, Ren X, Galbo PM, Moerdler S, Wang H, Sica RA, Etemad-Gilbertson B, Shi L, Zhu L, Tang X, Lin Q, Peng M, Guan F, Zheng D, Chinai JM, Zang X. KIR3DL3-HHLA2 is a human immunosuppressive pathway and a therapeutic target. Science Immunology, 6:eabf9792, 2021.

Nishimura CD, Pulanco MC, Cui W, Lu L, Zang X. PD-L1 and B7-1 cis-interaction: New mechanisms in immune checkpoints and immunotherapies. Trends in Molecular Medicine, 27:207-219, 2021.