Session 6 – Protein Drugs and Combination Products
Date: 25 July (Thursday) 14:00 – 17:30 Venue: 3F, Bldg. A, CTBC Financial Park, Ballroom B
Alice Lin-Tsing Yu
Distinguished Chair Professor
Chang Gung University
Dr. Alice Yu is an Academician, a Distinguished Professor & Co-Director of the Institute of Stem Cell & Cancer Translational Research in Chang Gung Memorial Hospital at Linko, Taiwan, and a Professor Emeritus at the University of California in San Diego. Formerly she was the Chief of Pediatric Hematology/Oncology at the University of California in San Diego, and Distinguished Research Fellow and Deputy Director of the Genomics Research Center of Academia Sinica in Taiwan.
Dr. Yu received her MD at the National Taiwan University Medical College, and a PhD in microbiology/ immunology at University of Chicago. She has received many awards including Academic Award from the Ministry of Education Wang Min-Ning Memorial Award for Outstanding Contribution to the Development Medical Science and Technology, National Health and Society, and “Key to Life” Award from the Leukemia & Lymphoma Society in USA, Excellence in Technology Transfer Award 2016 from Federal Laboratory Consortium, USA: “Discovery to Commercialization: New Immunotherapy for Rare Childhood Cancer, Neuroblastoma”, etc..
Session Speech Title & Synopsis: Overview of Immuno-Oncology: Possibilities and Challenge
Host immunity recognizes and eliminates most tumor cells in early stage of tumor development, but immune checkpoint molecules, such as CTLA-4, PD-1, and PD-L1, allow tumor cells to evade antitumor immune responses by blocking T cell activation. The mechanistic basis of immuno-oncology therapy is to target immunological escape processes regulated by the immune checkpoint receptors and ligands to facilitate immune activation and extend patient survival. Recent approval of six agents by the US Food and Drug Administration (FDA) to block CTLA-4 and PD-1/PD-L1 pathway for treatment of 13 cancer types has yielded unprecedented clinical success, providing new hope for cancer cure. However, only a minority of patients exhibit durable responses and significant immune-related adverse events occur in some patients. Identification of effective predictive markers such as tumor infiltrating immune cells, PD-L1 expression, tumor mutation burden, and tumor genetic and epigenetic signatures remain an active area of research.
Another class of immune modulatory molecules is cancer associated glycosphingolipids (GSL) such as GD2, Globo H. GD2 is overexpressed in many neuroectodermal cancers, including neuroblastoma, melanoma, small cell lung cancer as well as in sarcomas. GD2-ceramide has been shown to inhibit T cell proliferation and impair differentiation of dendritic cells. Globo H is the most prevalent cancer associated glycans, overexpressing in a variety of epithelial cancers including cancers of breast, lung, ovary, endometrium, stomach, colon, liver, etc.. Similar to GD2, Globo H ceramide also acts as an immune-checkpoint by suppressing T and B cell functions. In addition, it can promote angiogenesis. These findings provide the rationales for developing immunotherapeutics targeting cancer associated GSL. Indeed, through the pioneer work of Dr. Yu and her leadership during the entire course of clinical development, a chimeric anti-GD2 antibody, Dinutuximab was approved for the treatment of high-risk neuroblastoma in 2015. This marks the first new agent targeting a glycolipid molecule, thereby widening the net of potential pharmaceutical targets. A multi-national phase II clinical trial of Globo H-KLH vaccine in breast cancer showed survival benefits for those patients who generated significant anti-Globo H antibody responses. A global phase III trial is now underway.