Title: Targeting LILRB family of receptors for cancer therapy

Presenter: Prof. Zhiqiang An

University: University of Texas Health Science Center

Time: 14:00-15:00, May 17, 2019

Venue: Room A102, Institute of Microbiology, Chinese Academy of Sciences

Abstract: Inhibitory leukocyte immunoglobulin-like receptors (LILRBs 1-5) transduce signals via intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that recruit protein tyrosine phosphatase non-receptor type 6 (PTPN6 or SHP-1), protein tyrosine phosphatase non-receptor type 11 (PTPN11 or SHP-2), or Src homology 2 domain-containing inositol phosphatase (SHIP), leading to negative regulation of immune cell activation. The activation of LILRBs on immune cells by their ligands may contribute to immune evasion by tumors. Several members of LILRB family are expressed by tumor cells, notably hematopoietic cancer cells, and may directly regulate cancer development and relapse as well as the activity of cancer stem cells. LILRBs thus have dual concordant roles in tumor biology – as immune checkpoint molecules and as tumor-sustaining factors. LILRBs thus represents a novel class of targets for cancer therapy.

Introduction of Presenter:

Dr. Zhiqiang An received his Ph.D. degree from the University of Kentucky and his postdoctoral training at the University of Wisconsin-Madison. Then, he started his biotech career at Millennium Pharmaceuticals. Later, he served as Chief Scientific Officer at Epitomics, Inc. and was Director of Biologics Research at Merck Research Laboratories. Currently, Dr. An is Professor of Molecular Medicine, the Robert A. Welch Distinguished University Chair in Chemistry, and Director of the Texas Therapeutics Institute at the University of Texas Health Science Center at Houston. His laboratory focuses on cancer antibody drug resistance mechanisms, biomarkers for cancer therapeutic antibodies, and antibody drug discovery targeting cancer and infectious diseases. Dr. An also directs the Therapeutic Monoclonal Antibody Lead Optimization and Development Core Facility funded by the Cancer Prevention and Research Institute of Texas (CPRIT).

Selected publications (Maximum 3 items)

1.      LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration. Nature, 2018, 562(7728):605-609.

2.      Glutamic acid-valine-citrulline linkers ensure stability and efficacy of antibody-drug conjugates in mice. Nature Communications, 2018, 9(1):2512.

3.      Complement enhances in vitro neutralizing potency of antibodies to human cytomegalovirus glycoprotein B (gB) and immune sera induced by gB/MF59 vaccination. NPJ vaccines, 2017, 2:36.