Albert Einstein College of Medicine

New York, USA

New Immune Checkpoints and Immunotherapies

From Discoveries to 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, HHLA2 and TMIGD2, identified the HHLA2-KIR3DL3 immunosuppressive pathway, identified the HHLA2-TMIGD2 immunostimulatory pathway, demonstrated the biology and therapeutic potential of the KIR2DL5-PVR pathway, and contributed to other immune checkpoints B7-H3, 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, structure, imaging, etc) to understand how new immune checkpoints regulate T cells, NK cells, and other immune cells. Current emphasis in the lab: new immune checkpoints and cancer immunotherapies,  autoimmune diseases and immunotherapies, metabolic diseases and immunotherapies.

A new immune checkpoint inhibitor from our lab is currently in several phase II and I/II clinical trials in patients with advanced solid tumors (nasopharyngeal cancer, head and neck cancer, non-small cell lung cancer, small cell lung cancer, esophageal cancer, melanoma) or recurrent/refractory hematologic malignancies (acute myeloid leukemia, myelodysplastic syndromes, lymphoma). Another novel first-in-class immune checkpoint inhibitor from our lab will start phase I, multicenter, first-in-human clinical trial in 2023. Our research has formed scientific foundation and core intellectual property for several start-up drug companies.

Since 2008 the lab has mentored 49 trainees of MD-PhD or PhD students, postdoctoral fellows, clinical fellows, and visiting scientists. Most of trainees have subsequently moved on to independent careers in academic universities, medical centers, biopharmaceutical industry, and US government agencies.