MS Analysis of immune checkpoint proteins in cancer

发布时间 :2018-11-12  阅读次数 :506

报 告  人:Prof. Daniel C. Liebler, 

Vanderbilt University School of Medicine, Nashville, TN, USA

President, Protypia, LLC, Brentwood, TN, USA 

报告时间:2018年11月13日 10:00am-11:00am
报告地点:闵行校区生物药学楼2-116

联 系  人:李婧, jing.li@sjtu.edu.cn

 

报告人介绍:

Prof. Daniel C. Liebler, Ph.D. is an internationally-recognized research leader in the fields of proteomics, cancer diagnostics and toxicology. With over 30 years experience at the interface of analytical technology, chemical biology and disease research, Dr. Liebler has led multidisciplinary programs funded by the National Institutes of Health, industry and private philanthropy. From 2006-2015, he Directed the Jim Ayers Institute for Precancer Detection and Diagnosis, a unique initiative to apply mass spectrometry-based proteomic technology to cancer diagnostics. Dr. Liebler also led the Vanderbilt programs in the National Cancer Institute Clinical Proteomic Tumor Analysis Consortium, which laid the groundwork for the integration of proteomic technologies into cancer diagnostics. Dr. Liebler has recently launched Protypia, LLC, which provides analytical solutions for drug safety evaluation and therapeutic development.

报告摘要:

New immunotherapeutic drugs targeting immune checkpoint proteins produce durable therapeutic responses in previously lethal cancers, including melanoma, non-small cell lung cancer, renal carcinoma, and other solid tumors and hematologic cancers.  However, less than half of patients typically respond to monotherapies and combinations of immune checkpoint inhibitors are undergoing clinical evaluation.  A key challenge is the heterogeneity of expression of immunotherapeutic drug targets.  The lack of target-based patient selection leads to expensive clinical trial failures.  We developed a targeted MS method to quantifiy programmed cell death-1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2) at fmol/microgram protein levels in formalin fixed, paraffin-embedded sections from 22 human melanomas.  PD-L1 MS measurements were largely concordant with immunohistochemistry (IHC) analysis of total PD-L1-positive cell content, except that highly glycosylated PD-L1 was not detectable by IHC. PD-L2 was present in half the samples at levels similar to PD-L1, which suggests that PD-L2, a higher affinity PD-1 ligand, may contribute to T-cell downregulation.  MS analyses quantified immune checkpoint/co-regulator proteins LAG3, IDO1, TIM-3, VISR and CD40, which displayed distinct expression independent of PD-1, PD-L1 and PD-L2.  Targeted MS provides a next-generation analysis platform to advance cancer immuno-therapeutics and diagnostics.  (Supported by NIH Grant U24CA159988)

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