THE ZANG LABORATORY
Albert Einstein College of Medicine
New York, USA
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New Immune Checkpoints and New Immunotherapies
From Fundamental Discoveries to Novel Drugs to New Clinical Trials
The immune system is determined by both positive costimulation and negative coinhibition. We discovered new members of the costimulatory/coinhibitory B7 family and CD28 family including B7x(B7-H4), 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, developed TOP CAR therapy, identified TMIGD2 and B7x as orchestrators on cancer stem cells, revealed B7-H3 as a metabolic regulator, and significantly contributed to other immune checkpoints Tim-3, ICOS, PD-L1/PD-1, BTNL2, etc. We use a variety of approaches (gene knock-out/transgenic mice, humanized mice, patient samples, monoclonal antibodies, single-cell RNA sequencing, protein/cell engineering, structure, in vitro/in vivo imaging, bioinformatics, etc) to understand how new immune checkpoints regulate T cells, NK cells, and other immune cells.
Current emphasis in the lab: 1) Fundamental biology of new immune checkpoints; 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 trial.
Our research has formed scientific foundation and core intellectual property for several drug companies.
Since 2008 the lab has mentored a total of 68 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 government agencies of the United States and Canada.
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