: Development of novel leads for triple-negative breast cancer immunotherapy

Title : : Development of novel leads for triple-negative breast cancer immunotherapy

Abstract:

Breast cancer ranks first of all cancers among women in the world in incidence and mortality. It is still on the rise year by year. Triple negative breast cancer (TNBC) comprises around 15~20% of breast cancers. It is characterized by a poor prognosis, high rates of proliferation and metastases. However, no FDA-approved targeted therapies are currently available for TNBC.
    CCL5 and CCR5 are highly expressed by breast tumor cells, and involved in the disease progression, relapse and metastasis, particularly in TNBC. Our previous work from a mouse TNBC model indicates that CCL5 induces immunosuppression principally by promoting the generation of myeloid-derived suppressor cells (MDSCs, CD11b⁺, Gr-1⁺), which accumulate in many cancer patients and exert a variety of immunosuppressive mechanisms. In addition, systemically blocking of CCL5 with a murine monoclonal antibody profoundly suppresses the primary mammary tumor growth. Our recent work has further conceptually demonstrated that the CCL5/CCR5 signaling axis in MDSCs represents an excellent target for TNBC immunotherapy. Inhibition of the CCL5/CCR5 axis in a mouse model of TNBC resulted in strong reductions of MDSCs and regulatory T cells, while increasing tumor-infiltrating CD8⁺ T cells and improving their cytotoxic potency. Moreover, we have developed a high-throughput screening assay for discovering novel antagonists of CCL5-CCR5 signaling. Through the screening of about 2,200 clinically approved drug, three drugs were identified. The new finding provides us the potential mechanism for these drugs in TNBC immunotherapy.
Audience take away:
• The new targets for TNBC immunotherapy. 
• The novel antagonists of CCL5-CCR5 signaling.
• New indications of three clinically used drugs on inhibiting the CCL5-CCR5 signaling. 

Biography:

Dr. Jing Yu received her PhD degree in drug discovery from the University of Basel (Switzerland) in 2008, and then she commenced her two-year postdoctoral work in drug delivery for delivery of large molecules (including cells & antibodies) at the University of Geneva (Switzerland). Now she is an Associate Professor at the Shanghai Jiao Tong University, China. Her research focuses on the drug discovery and mechanism studies of lead compounds for novel drug targets, as well as drug delivery. Her original research works have been published in the top journals of these fields. In addition, she has applied for 5 patents and all of them have been authorized from China and the United Kingdom now.