Mei Zhang

Biography

Research Assistant Professor Assistant Professor, Biomedical Engineering

Research Interest

Our research program focuses on research and clinical development of immunotherapy for cancers. Cancer cells are highly heterogeneous, making them notoriously difficult to target. Increasing evidence has shown that macrophage infiltrates and accumulates at specific “niches” of tumor tissue and plays a significant role for tumor growth and metastasis. The cytokine milieu in tumor drives monocytes/macrophages to express specialized and polarized functional properties (M1 and M2 paradigm). M1 macrophages are professional phagocytes and antigen presentation cells. They can engulf transformed cells and mediate adaptive immunity, thus, exert anti-tumor activity and correlates with better prognosis. M2 activated TAMs promote angiogenesis, mediate immune suppression and inhibit the development of innate and adaptive immunity, thus, exert tumor-promoting activity and correlate with poor prognosis. The strong immune suppression mediated by M2-TAMs has been considered to be the major factor that limits the efficacy of many types of therapies including chemotherapies, cellular immunotherapies, and other therapies in trials. Based upon this, we aim to develop innovative nanotechnology and gene therapy that can specifically target, imaging, assess and manipulate M2-TAMs in tumor microenvironment. This anticipates to establishing an environment that is favorable for patient to develop tumor-specific immune responses. In addition, we currently have one ongoing phase I clinical trial of adoptive Immunotherapy for Stage III/IV melanoma patients (led by Dr. Julian Kim, Division of Surgical Oncology). Studies for the past decades have demonstrated that T cells with a specific inhibitory effect on cancer cells were present in patients with advanced cancer and could be used as potential candidate for adoptive immunotherapy. Recent clinical trials have demonstrated that adoptive immunotherapy using ex vivo activated T cells can result in regression of bulky metastatic disease in patients with metastatic cancer. The durable complete responses have not been replicated with any other type of therapy so far. In our clinical trial of Case 3612, we aim to develop ex vivo-expanded melanoma-specific stem-like CD4+ T cells from melanoma draining lymph nodes, which anticipates to mediating durable immune responses upon adoptive administration.