The immune system is determined by both positive costimulation and negative coinhibition, generated mainly by the interaction between the B7 ligand family and their receptor CD28 family. We discovered new members of the T cell costimulatory/coinhibitory B7 family and CD28 family including B7x, HHLA2 and TMIGD2, discovered the HHLA2-KIR3DL3 immunosuppressive pathway, discovered the HHLA2-TMIGD2 immunostimulatory pathway, demonstrated the biology and therapeutic potential of the KIR2DL5-PVR pathway, and significantly contributed to other immune checkpoints B7-H3, Tim-3, ICOS, PD-L1/PD-1, BTNL2, etc. We are using a variety of experimental approaches (gene knock-out/transgenic mice, humanized mice, monoclonal antibodies, single-cell RNA sequencing, protein/cell engineering, structure, patients samples, in vitro/in vivo imaging, bioinformatics, etc) to understand how new immune checkpoints regulate T cells and other immune cells.
Current emphasis in the lab is placed in the following areas: 1) Fundamental biology of new immune checkpint pathways; 2) Translational immunotherapies in cancers, autoimmune diseases, metabolic diseases.
A new immune checkpoint inhibitor from our lab is currently in nine clinical trials of phase II and I/II in 695 patients with 8 different types of advanced solid cancers (nasopharyngeal cancer, head and neck cancer, hepatocellular carcinoma, non-small cell lung cancer, small cell lung cancer, esophageal cancer, melanoma, colorectal cancer) and 3 different types of recurrent/refractory hematologic cancers (acute myeloid leukemia, myelodysplastic syndromes, lymphoma).
Another novel first-in-class immune checkpoint inhibitor from our lab is currently in phase I, multicenter (Massachusetts General Hospital, MD Anderson Cancer Center, Johns Hopkins University, Montefiore Einstein Cancer Center, Sarah Cannon Research Institute, NEXT Oncology-San Antonio), first-in-human clinical trial in 131 patients with 12 different types of metastatic solid cancers (pancreatic cancer, cholangiocarcinoma, renal cell carcinoma, non-small cell lung cancer, triple negative breast cancer, prostate cancer, colorectal cancer, urothelial carcinoma, gastric gastroesophageal carcinoma, endometrial cancer, cervical cancer, osteosarcoma).
Guided by our basic discoveries, a new antibody drug was developed and is currently in phase I clinical trial.
Our research has formed scientific foundation and core intellectual property for several drug companies.
Since 2008 the lab has mentored a total of 65 trainees, including PhD and MD-PhD students, postdoctoral fellows, clinical fellows, and visiting scientists. Most of these trainees have progressed to successful careers at academic universities, medical centers, biopharmaceutical industry, and US government agencies.
Zang Lab website:
https://www.xingxingzanglab.org
